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XVIIKU FARMA
T O K ST ræf for3
1
O rganisk16
8
K
emi-39
19
S
tuderende32
16
Department of Drug Design and Pharmacology
University of Copenhagen
May 3rd & 4th 2019
We kindly thank to our sponsors who made TOKS XVII possible!
SPONSORS
Friday 3rd of May
1100
Registration, networking and sandwiches
(outside Auditorium 4)
1200
Opening of TOKS XVII
Session 1: Synthesis and Application of
Biomolecules (sponsored by DRA)
1215
Introduction
Prof. Kristian Strømgaard
University of Copenhagen
1230
Prof. Jean-Louis Reymond
University of Bern
“Fighting Multidrug Resistant Bacteria with Peptide
Dendrimers and Bicyclic Peptides”
1330
Dr. Laurence Mulard
Pasteur Institute Paris
“Chemical Biology Strategies for the Development
of Innovative Carbohydrate-based Bacterial
Vaccines”
1425
Coffee Break
1450
Prof. Karl-Heinz Altmann,
ETH Zurich
“The Chemistry and Biology of the Marine
Macrolides Zampanolide and Dactylolide”
1545
Closing remarks of Session 1
Session 2 (Student talks and poster
session)
1600
Bengt Gless (KU FARMA)
“Identification of Autoinducing Thiodepsipeptides
from Staphylococci Enabled by Native Chemical
Ligation”
1620
Tiago Bozzola (Lund University)
“Synthesis of C3 and C9 sialic acid derivatives as
ligands to the bacterial sodium solute symporter
from P. mirabilis”
1640
Eduardo F. A. Fernandes (KU FARMA)
“A Peptide Radioligand for Molecular Imaging of
Postsynaptic Density Scaffolding Proteins in the
Brain”
1700
Poster session and refreshments (Atrium).
Complimentary beers and soft drinks
1900
– 0200
Dinner and party (FARMA canteen
and Atrium)
Saturday 4th of May
930
Coffee (outside Auditorium 4)
Session 3 (Student talks II and plenary
lecture from Danish biotech)
1000
Michael M. Nielsen (KU KEMI)
“Reinvestigation of C-F Bond Activation in
Carbohydrate Chemistry”
1020
Esmeralda Bukuroshi (KU KEMI)
“Fluorinated Boron Subphthalocyanines:
Clarification on the Chemistry, Full Fluoride
Exchange Process, Property Assessment and
Further Derivatization”
1040
Aske S. Donslund (Aarhus University)
“Direct Access to β-ketonitriles via Nickel-
Catalyzed Carbonylative Coupling of α-
bromonitriles with Alkylzinc reagents”
1100
Erik Funder
Senior Research Scientist
Roche Innovation Center Copenhagen
“Discoveries within LNA Phosphorothioate
Oligonucleotides”
Session 4 (Student talks III)
1330
Katrine Domino (Aarhus University)
“Direct Access to Aryl Bis(trifluoromethyl)carbinols
from Aryl Bromides or Fluorosulfates via
Palladium-Catalyzed Carbonylation”
1350
Frederik Rostrup (KU – FARMA)
“The yet unidentified DS2 binding site – An update
report”
1410
Esben B. Svenningsen (Aarhus University)
“Establishing Cell Painting at Aarhus University”
1430
Group picture
1440
Closing remarks and prize awards
1500
End of TOKS XVII
1200
Pizzas and posters (Atrium)
Prof. Dr. Jean-Louis Reymond Jean-Louis Reymond is professor of chemistry and chemical
biology at the University of Bern, Switzerland. He studied chemistry
and biochemistry at the ETH Zürich and obtained his PhD in 1989
at the University of Lausanne on natural products synthesis. After a
post-doc and assistant professorship at the Scripps Research
Institute, he joined the University of Bern in 1997. His research
focuses on expanding the accessible chemical space to novel
scaffolds for drug design, including the synthesis of topologically
diverse peptides such as dendrimers and polycyclic peptides
identified by combinatorial library screening and computational
design, and of innovative small molecules identified by virtual screening of the chemical universe
database GDB (www.gdb.unibe.ch). He is the author of over 250 scientific publications and
reviews.
Dr. Laurence Mulard Dr. Mulard is a Deputy Director at the Institut Pasteur, Paris. She
obtained her PhD in Medicinal Chemistry at the University of Paris.
In 1991 Mulard has been awarded an NIH post-doctoral fellowship
and moved to Bethesda, MD, USA where she focused on
Glycosciences at National Institute of Diabetes and Digestive and
Kidney Diseases. Three years later she returned to Europe and
started her career at the Institut Pasteur as a research assistant
and later research scientist. Since 2015 Laurence Mulard has been
appointed as a Deputy Director, her current major focus is on the
synthesis of well-defined mimics of selected bacterial
polysaccharides – and conjugates thereof – for the development of carbohydratebased probes
and/or tools of interest for biological investigations and carbohydrate-based vaccines.
KEYNOTE SPEAKERS
Prof. Dr. Karl-Heinz Altmann
Karl-Heinz Altmann has been a Professor of Pharmaceutical
Sciences at the Swiss Federal Institute of Technology (ETH) in
Zürich since July 2003. Professor Altmann studied Chemistry at the
University of Mainz, Germany and he holds a PhD degree in
Organic Chemistry from the University of Basel, Switzerland. From
1990 to 1996 he was a research scientist and group leader at Ciba-
Geigy Central Research in Basel. In 1997 he moved to Novartis
Pharma and worked as a project leader in Oncology Research,
later in 2000 Karl-Heinz Altmann was appointed the Novartis Senior
Chemistry. In 2014 Professor Altmann was awarded the Paul
Ehrlich Prize of the Société de Chimie Thérapeutique, France. Prof. Altmann serves on a number
of scientific advisory boards and as consultant to different pharmaceutical companies. Research in
the Altmann group is centered on the chemical synthesis of pharmaceutically relevant natural
products/ natural product analogs and their biological evaluation, with a particular focus on leads
for anticancer and antituberculosis drug discovery.
Dr. Erik Daa Funder
Erik Funder is a senior scientist at Roche Innovation Center
Copenhagen. Funder started his career with PhD studies in
Chemistry in the group of Prof. Dr. Kurt V. Gothelf at University of
Aarhus, Denmark. During his PhD he spent seven months at The
Scripps Research Institute in the Prof. Phil S. Baran lab as a visiting
PhD student. After graduating in 2013 he did a post-doctoral study
at Department of Chemistry and iNANO, Aarhus University. In 2014
he moved to Switzerland, ETH Zurich, where he worked as a
Postdoc at Laboratory of Organic Chemistry, focusing on synthesis
and optimization of functionalized steroids for diabetes II
suppression, and the development of new oxidation methodology. His research at Roche
Innovation Center Copenhagen is centered on the synthesis and optimization of new chemistry
within therapeutic oligonucleotides.
KEYNOTE SPEAKERS
FIGHTING MULTIDRUG RESISTANT BACTERIA WITH PEPTIDE DENDRIMERS AND
BICYCLIC PEPTIDES
Jean-Louis Reymond.
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland. jean-
There is an urgent need to develop new antimicrobial agents to fight multidrug resistant (MDR)
bacteria, which represent a public health threat in the hospital environment worldwide. My group
focuses on Gram-negative MDR strains of Pseudomonas aeruginosa, Acinetobacter baumannii,
Escherichia coli and Klebsiella pneumoniae, which are particularly problematic. In this lecture, I will
discuss the experiments that led us from our initial studies with antibiofilm dendrimer agents
identified by combinatorial chemistry approaches,[1] to our latest antimicrobial peptide dendrimers[2]
cyclic[3] and bicyclic peptides[4] identified using an innovative chemical space guided discovery
strategy.[5] I will also discuss structure-function relationships in our peptide dendrimers and bicyclic
peptides.
[1] G. Michaud, R. Visini, M. Bergmann, G. Salerno, R. Bosco, E. Gillon, B. Richichi, C. Nativi, A. Imberty, A.
Stocker, T. Darbre, J.-L. Reymond, Chem. Sci. 2016, 7, 166-182.
[2] a) T. N. Siriwardena, M. Stach, R. He, B. H. Gan, S. Javor, M. Heitz, L. Ma, X. Cai, P. Chen, D. Wei, H. Li, J.
Ma, T. Kohler, C. van Delden, T. Darbre, J. L. Reymond, J. Am. Chem. Soc. 2018, 140, 423-432; b) T. N.
Siriwardena, A. Capecchi, B. H. Gan, X. Jin, R. He, D. Wei, L. Ma, T. Kohler, C. van Delden, S. Javor, J. L.
Reymond, Angew. Chem., Int. Ed. Engl. 2018, 57, 8483-8487.
[3] R. He, I. Di Bonaventura, R. Visini, B.-H. Gan, Y. Fu, D. Probst, A. Luscher, T. Kohler, C. van Delden, A.
Stocker, W. Hong, T. Darbre, J.-L. Reymond, Chem. Sci. 2017, 8, 7464-7475.
[4] a) I. Di Bonaventura, X. Jin, R. Visini, D. Probst, S. Javor, B.-H. Gan, G. Michaud, A. Natalello, S. M. Doglia, T.
Kohler, C. van Delden, A. Stocker, T. Darbre, J.-L. Reymond, Chem. Sci. 2017, 8, 6784-6798; b) I. Di
Bonaventura, S. Baeriswyl, A. Capecchi, B.-H. Gan, X. Jin, T. N. Siriwardena, R. He, T. Kohler, A. Pompilio, G.
Di Bonaventura, C. van Delden, S. Javor, J.-L. Reymond, ChemComm 2018, 54, 5130-5133.
[5] A. Capecchi, M. Awale, D. Probst, J. L. Reymond, Mol. Inform. 2019, doi: 10.1002/minf.201900016.
Chemical space of
bicyclic peptides
bp56
MIC = 4 g/mL
(A. baumannii)
MIC = 8 g/mL
(P. aeruginosa)
REYMOND
CHEMICAL BIOLOGY STRATEGIES FOR THE DEVELOPMENT OF INNOVATIVE
CARBOHYDRATE-BASED BACTERIAL VACCINES
Laurence Mulard
Institut Pasteur Laboratory “Chemistry of Biomolecules”
28 rue du Dr Roux, 75 724 Paris Cedex 15, France
Glycans – also known as carbohydrates – are ubiquitous in nature. Surface glycans provide a cell with specific identity and play key roles in many biological processes, among which the host-pathogen crosstalk. The human immune system has evolved the ability to recognize pathogen-specific glycans on bacteria, triggering an immune response. On that basis, bacterial capsular polysaccharides have been used as effective vaccines for adults. To answer the need for infant and senior vaccination, conjugate vaccines composed of bacterial capsular polysaccharides covalently attached to protein carriers were developed successfully. However, there is yet no vaccine available for non-capsulated bacteria. The use of synthetic oligosaccharides equipped for single site attachment to a carrier was proposed as an attractive alternative to the use of polysaccharides from biological sources. These strategies, with emphasis on the latest approach, will be exemplified in the context of shigellosis, or bacillary dysentery, one of the most devastating diarrheal diseases in children under five years of age.1
Shigellosis is caused by the non-capsulated enteroinvasive bacteria Shigella.1 Species/serotype diversity and geographical distribution strongly support the need for a multivalent Shigella vaccine.
In the search for a highly immunogenic vaccine able to generate protective immunity providing broad species and serotype coverage in young children against shigellosis, a multidisciplinary strategy interfacing chemical biology and structure-based vaccinology was implemented. It consists firstly in the identification of sets of “protective” epitopes by use of a diversity of well-defined synthetic oligosaccharides representing fragments of the polysaccharide of interest. Panels of protein conjugates of the most promising oligosaccharides are then synthesized and evaluated for their immunogenicity in mice. A tetanus toxoid conjugate encompassing a synthetic glycan corresponding to three basic repeating units of the polysaccharide from S. flexneri 2a, the most prevalent Shigella serotype, was shown to induce polysaccharide bactericidal antibodies in preclinical studies.2 A GMP batch was produced and a first-in-human, single-blinded, observer-masked randomized, dose escalation, placebo-controlled study was conducted to assess safety and immunogenicity in healthy adult volunteers.3
This presentation provides an overview of our chemistry-based strategy for a broad coverage Shigella vaccine. Emphasis is on epitope mapping with special interest in chain length, endchain residue, non-stoichiometric substitutions and glycan:carrier ratio toward glycan selection, glycoconjugate vaccine design and production of a GMP batch. Safety and immunogenicity data following first use in human are exposed.
Promising data in human strongly support further developments of this novel strategy toward
vaccines against bacterial diseases. References
[1] J. Liu, et al., Lancet 2016, 388, 1291-1301.
[2] R. van der Put, et al., Bioconjugate Chem 2016, 27, 883-892.
[3] https://clinicaltrials.gov/ct2/show/NCT02797236.
MULARD
THE CHEMISTRY AND BIOLOGY OF THE MARINE MACROLIDES
ZAMPANOLIDE AND DACTYLOLIDE
Karl-Heinz Altmann Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, HCI
H405, Vladimir-Prelog-Weg 4 Email: [email protected]
Zampanolide (1) is a marine NP that was first reported in 1996 by Tanaka and Higa[1] and shown to be a potent inhibitor of tumor cell proliferation in vitro. In 2009, it was re-extracted from the Togan sponge Cacospongia mycofijiensis by Northcote, Miller, and co-workers, who confirmed its antiproliferative activity and uncovered its microtubule-stabilizing and tubulin-polymerizing effects.[2] In 2001, the group of Riccio reported a macrolactone structurally related to zampanolide (1) that had been isolated from the sponge Dactylospongia sp. and that was termed dactylolide (2).[3]
(-)-Zampanolide (1) (+)-Dactylolide (2)
In contrast to 1, dactylolide (2) is only a moderately potent antiproliferative agent, with IC50’s in the low mM range and the absolute configuration of 2 is opposite to the configuration of the macrolactone core in 1;[4] in fact, ent-2, whose configuration corresponds with that of the macrolactone core in zampanolide (1), was first isolated from natural sources only very recently.[5]
Before this background, we have developed convergent total syntheses of 1 and 2, which have enabled a range of biochemical and structural studies. At the same time, the total synthesis work has established a platform for the synthesis of analogs for SAR studies. After a summary of the total synthesis work and the biological and structural studies with 1 and 2, this contribution will discuss the synthesis and biological activity of a series of zampanolide and dactylolide analogs.
[1] J.-i. Tanaka, T. Higa, Tetrahedron Lett., 1996, 37, 5535–5538. [2] J. J. Field, A. J. Singh, A. Kanakkanthara, T. Halafihi, P. T. Northcote, J. H. Miller, J. Med. Chem., 2009, 52, 7328 –
7332. [3] A. Cutignano, I. Bruno, G. Bifulco, A. Casapullo, C. Debitus, L. Gomez-Paloma, R. Riccio, Eur. J. Org. Chem., 2001,
775–778. [4] A. B. Smith, III, I. G. Safonov, Org. Lett., 2002, 4, 635–637. [5] T. Taufa, A. J. Singh, C. R. Harland, V. Patel, B. Jones, T. Halafihi, J. H. Miller, R. A. Keyzers, P. T. Northcote, P. J.
Nat. Prod., 2018, 81, 2539-2544
ALTMANN
IDENTIFICATION OF AUTOINDUCING THIODEPSIPEPTIDES FROM
STAPHYLOCOCCI ENABLED BY NATIVE CHEMICAL LIGATION
Bengt H. Gless1, Martin S. Bojer
2, Pai Peng
2, Mara Baldry
2, Hanne Ingmer
2,
Christian A. Olsen1
1Department of Drug Design and Pharmacology, University of Copenhagen.
2Department of Veterinary and Animal Sciences, University of Copenhagen.
Staphylococci secrete autoinducing peptides (AIPs) as signaling molecules to communicate from
cell-to-cell and to change population wide behavior, such as virulence gene expression.[1] The
inhibition of quorum sensing (QS) in the human pathogen Staphylococcus aureus represents an
promising approach towards anti-virulence treatments.[2] AIPs from non-aureus staphylococci are
often cross-species inhibitory[3,4] and have received attention as potential anti-virulence agents.
However, a limited number of AIP structures from non-aureus staphylococci have been identified to
date as the minute amounts secreted in complex media renders it difficult. Here, we present a
method for the identification of AIPs by exploiting their thiolactone functionality for chemoselective
trapping through native chemical ligation and enrichment from bacterial supernatant.[5] Standard
LC-MS analysis, guided by genome sequencing data of the AIP precursor peptide, readily provides
the AIP identities. By using this approach, the identities of 5 known AIPs were confirmed and the
AIPs of 11 non-aureus species were identified for the first time. All newly identified AIPs were
synthesized and evaluated for their ability to modulate QS in S. aureus, which revealed the first
staphylococcal inter-species activators and several promising inhibitor candidates.
[1] B. Wang, T. W. Muir, Cell Chem. Biol. 2016, 23, 214-224. [2] S. W. Dickey, G. Y. C. Cheung, M. Otto, Nat. Rev. Drug Discov. 2017, 16, 457-471.
[3] J. Canovas, M. Baldry, M. S. Bojer, P. S. Andersen, B. H. Gless, P. K. Grzeskowiak, M. Stegger, P. Damborg, C. A. Olsen, H. Ingmer, Front. Microbiol. 2016, 7, 1733. [4] B. H. Gless, P. Peng, K. D. Pedersen, C. H. Gotfredsen, H. Ingmer, C. A. Olsen, Org. Lett. 2017, 19, 5276-5279. [5] B. H. Gless, M. S. Bojer, P. Peng, M. Baldry, H. Ingmer, C. A. Olsen, Nat. Chem. 2019, in press.
STUDENT TALK 1
SYNTHESIS OF C3 AND C9 SIALIC ACID DERIVATIVES AS LIGANDS TO THE
BACTERIAL SODIUM SOLUTE SYMPORTER FROM P. MIRABILIS
T. Bozzola,a U. Ellervik,
a U. J. Nilsson
a
. aCentre for Analysis and Synthesis, Lund University, Sweden 22100
According to the World Health Organization (WHO), antibiotic resistance is a serious threat to our society. Infections with multi-resistant bacteria are causing increased mortality and social costs. Few new drugs are in the pipeline and no prospective of significantly improving the situation seems to be present. Due to the significance of sialic acid for bacterial growth and proliferation, the sialic acid uptake inhibition could represent a potent and novel pathway to develop new antibacterial drugs. A recently published bacterial (P. mirabilis) Sodium Solute Symporter (SSS) crystal structure has opened up the way for structure-guided design of sialic acid derivatives as inhibitors.
Here we present the design, synthesis, and evaluation of C-3 and C-9 sialic acid derivatives in order to gain a deeper understanding of the Structure-Activity Relationships in inhibiting the SSS protein. Evaluation of binding to the SSS protein with nano Differential Scanning Fluorimetry (nanoDSF) and Isothermal Titration Calorimetry (ITC) revealed novel compounds that bind with potency almost equal to that of the endogenous substrate, in the low micromolar range.
[1] WHO. Antimicrobial resistance. Global Report on Surveillance. Bull. World Health Organ. (2014) 61, 383–94. [2] Vimr, E. Unified theory of bacterial sialometabolism: how and why bacteria metabolize host sialic acids. ISRN Microbiol., (2013) 816713. [3] Wahlgren, W. Y. et al. Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new
Na+ site. Nat. Commun. (2018) 1–14.
STUDENT TALK 2
A PEPTIDE RADIOLIGAND FOR MOLECULAR IMAGING OF POSTSYNAPTIC
DENSITY SCAFFOLDING PROTEINS IN THE BRAIN
Eduardo F. A. Fernandes*a, Mikael Palner, Troels E. Jeppesen, Simone L. Bærentzen, Hans M. Maric,
Sören Doose, Andreas Kjær, Andreas Schlosser, Linda M. Haugaard-Kedström, Matthias M. Herth, Kristian
Strømgaard. aCenter for Biopharmaceuticals, Department of Drug Design and Pharmacology, University of
Copenhagen, Copenhagen 2100, Denmark. *[email protected]
The postsynaptic density (PSD) is a protein-rich subcellular region located adjacent to the
postsynaptic membrane of excitatory neurons.1 Mass-spectrometry and super-resolution
microscopy studies described more than 1000 PSD proteins organized in a laminar architecture.2
The PSD scaffolding proteins (PSPs) are placed in a central position at the PSD and are key to
synaptic transmission and plasticity, two fundamental molecular mechanisms of learning and
memory formation.3
In our work, we describe a high-affinity radioligand targetting the membrane-associated guanylate
kinase (MAGUK) class of PSPs. We first prepared a 18F labeled probe, obtained with >95%
radiochemical purity and molar activity ranging between 5-10 GBq/µmol. Autoradiography images
of rat brain slices displayed a differential distribution of radiation density (Figure 1). Cortex,
hippocampus, cerebellum and caudate-putamen regions exhibited higher specific binding than in
striatum, which correlated well with the known MAGUK brain distribution. The selectivity profile of
our tracer was evaluated by a proteomic analysis of pulled-down proteins of whole rat brain lysates
using the binding epitope of our tracer as bait. We obtained significant and selective enrichment of
the following PSPs: PSD-95, PSD-93, SAP-97, and SAP-102. Finally, positron emission
tomography (PET) images displayed low tracer uptake in the brain and a fast washout through the
kidneys. We envision that this probe is a valuable tool for in vitro brain imaging studies of PSPs in
the brain and for the future development of new and improved PET imaging radioligands.
Figure 1. Autoradiography images of our tracer in rat brain slices
[1] S. L. Palay, J Biophys Biochem Cytol 1956, 2, 193-202. [2] M. O. Collins, H. Husi, L. Yu, J. M. Brandon, C. N. Anderson, W. P. Blackstock, J. S. Choudhary, S. G. Grant, J Neurochem 2006, 97 Suppl 1, 16-23. [3] G. M. Elias, L. Funke, V. Stein, S. G. Grant, D. S. Bredt, R. A. Nicoll, Neuron 2006, 52, 307-320;
STUDENT TALK 3
Michael M. Nielsen,a Yan Qiao,
b Xianglin Hou,
b Yingxiong Wang,
b and Christian M. Pedersen
a.
aDepartment of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen O, Denmark.
bInstitute of Coal Chemistry, Chinese Academy of Sciences, 27 South Taiyuan Road, Taiyuan 030001,
People’s Republic of China.
Glycosyl fluorides have been amongst the most common electrophiles for catalytic glycosylations
since their introduction by the Mukaiyama group in 1981.[1,2]
Despite the extensive use of glycosyl fluorides in carbohydrate chemistry, the formation of
hydrogen fluoride as a byproduct in the reaction has generally been ignored in the literature.
In an attempt to understand whether the formation and persistence of HF had any effect on the
reaction, a series of experiments were carried out in regular glassware and in Teflon, an HF-
resistant material. The initial hypothesis was that the reaction would be faster in regular glassware
as consumption of HF by the SiO2 glass surface would drive the reaction towards completion.
Surprisingly, it was found that reactions in Teflon were in fact faster than reactions under similar
conditions in glass. Also, it was found that the reactions in Teflon gave rise to higher yields and
less byproduct formation despite accumulating hydrogen fluoride.
But why? Combined with an in-depth low-temperature 1H- and 19F-NMR investigation and isolated
byproducts, an explanation for this difference in reactivity and yield has been found.
[1] Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 10, 431–432 [2] Nielsen, M. M.; Pedersen, C. M. Chem. Rev. 2018, 118, 8285–8358
STUDENT TALK 4
FLUORINATED BORON SUBPHTHALOCYANINES: CLARIFICATION ON THE CHEMISTRY, FULL FLUORIDE EXCHANGE PROCESS, PROPERTY ASSESSMENT
AND FURTHER DERIVATIZATION
Esmeralda Bukuroshia, Amir Mizrahi
b, Jenya Vestfrid
a, Anne Petersen
c, Zeev Gross
b, Mogens Brønsted
Nielsenc and Timothy P Bender
a,d,e,
a Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street,
Toronto, Ontario, Canada M5S 3E4. b Schulich Faculty of Chemistry, Israel Institute of Technology
(Technion), Haifa 3200008, Israel. c Department of Chemistry, University of Copenhagen, Universitetsparken
5, DK-2100 Copenhagen Ø, Denmark. d Department of Chemistry, University of Toronto, 80 St George
Street, Toronto, Ontario, Canada M5S 3H6.e Department of Materials Science and Engineering, University of
Toronto, 184 College Street, Toronto, Ontario, Canada, M5S 3E4.
A member of the phthalocyanine family, boron subphthalocyanine (BsubPc) has robust chemistry
and can be readily modified chemically at the axial and peripheral position to tune the physical and
electronic properties for organic solar cell (OSC) applications.1 Our laboratory recently discovered
that peripheral chlorination (replacing all peripheral hydrogens with chlorines) of BsubPcs
facilitates the harvesting of triplets from the singlet fission process in OSCs, that can theoretically
enable them to exceed 100% light conversion efficiency.2 Owing to this significance, we are
investigating the effect of peripheral fluorination vs chlorination on OSC performance. Here we
report our efforts to simplify the process for making Cl-F12BsubPc and Cl-F6BsubPc. In our hands,
both processes indicated random formation at varying degrees of the axially fluoro-BsubPc
derivatives, in addition to the chloro-BsubPcs of interest. These findings lead us to scope synthetic
methods for completing the axial fluorination of these BsubPcs yielding F-F12BsubPc and F-
F6BsubPc. We report the optimized synthetic procedure for the axial fluorinated BsubPcs, one of
which (F-F6BsubPc) has no precedence in the literature. These BsubPcs were procured at high
purity via train sublimation. The structure of these compounds was analyzed by 1H, 13C, and 19F
NMR spectroscopy, elemental analysis, mass spectrometry and x-ray crystallography. Other
structure-property relations were assessed by cyclic voltammetry, UV/Vis and photoluminescence
spectrometry. The solid-state arrangement of F-F6BsubPc and F-F12BsubPc was compared against
the chlorinated analogs, Cl-Cl6BsubPc and Cl-Cl12BsubPc. The ongoing project in Denmark
includes fictionalizing these fluorinated BsubPcs at the axial position to study other unique
properties.
[1] Morse et al, ACS Applied Materials & Interfaces 2012, 4 (10), 5055-5068. [2] Castrucci et al, The Journal of Physical Chemistry Letters 2015, 6 (15), 3121-3125.
STUDENT TALK 5
DIRECT ACCESS TO β-KETONITRILES VIA NICKEL-CATALYZED CARBONYLATIVE
COUPLING OF α-BROMONITRILES WITH ALKYLZINC REAGENTS
Aske S. Donslund, Karoline T. Neumann, and Troels Skrydstrup.
Department of Chemistry and the Interdisciplinary Nanoscience Center (iNANO), University of Aarhus,
Gustav Wieds Vej 14, 8000, Denmark. [email protected]
Herein, we describe the development of a nickel(II)-catalyzed carbonylative coupling of alkylzinc
reagents and α-bromonitriles to afford β-ketonitriles in good yields under mild conditions. Key to
the success of this carbonylative chemistry is the readily available nickel(II) chloride pincer
complex, which forms stable nickel(II) alkyl and nickel(II) acyl complexes as observed by 1H- and 13C-NMR spectroscopy.
The combined use of the two-chamber system, COware® and the carbon monoxide releasing
molecule, COgen, for ex situ generation of carbon monoxide, enabled a successful carbonylation.[1]
β-Ketonitriles are versatile precursors for the synthesis of heterocycles, and as such, by using 13COgen in the three-component coupling, access to 13C-isotopically labeled β-ketonitriles was
obtained, and their corresponding isotopically labeled heterocycles. Initial mechanistic
investigations suggest the presence of radical intermediates.[2]
[1] S. D. Friis, A. T. Lindhardt, T. Skrydstrup, Acc. Chem. Res. 2016, 49, 594.
[2] A. S. Donslund, K. T. Neumann, N. P. Cornelisussen, E. K. Grove, D. Herbstritt, K. Daasbjerg, T. Skrydstrup, Manuscript in preparation.
STUDENT TALK 6
DIRECT ACCESS TO ARYL BIS(TRIFLUOROMETHYL)CARBINOLS FROM ARYL
BROMIDES OR FLUOROSULFATES VIA PALLADIUM-CATALYZED
CARBONYLATION
Katrine Domino, Cedrick Veryser, Benjamin A. Wahlqvist, Cecilie Gaardbo, Karoline T. Neumann, Kim
Daasbjerg, Wim M. De Borggraeve and Troels Skrydstrup.
Carbon Dioxide Activation Center (CADIAC), Department of Chemistry and The Interdisciplinary
Nanoscience Center (iNANO), Aarhus University,
Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
The bis(trifluoromethyl)carbinol unit represents an important constituent of biologically active
compounds employed in the treatment of diseases such as hepatitis C, cancer and diabetes, and
their high number of fluorine atoms makes them useful as potential contrast agents for 19F-MRI.
Furthermore, polymers containing aryl bis(trifluoromethyl)carbinol structures are used in materials
because of their high thermal stability and flame resistance.
In this work, we have developed a mild and efficient protocol for the selective introduction of
bis(trifluoromethyl)carbinols onto an aromatic core starting from their corresponding (hetero)aryl
bromides or fluorosulfates. The methodology operates via a palladium-catalyzed carbonylation and
employs only stoichiometric amounts of carbon monoxide and the Ruppert-Prakash reagent.
Furthermore, the procedure proved tolerant to a variety of functional groups thereby allowing for
the direct and late-stage carbon isotope-labeling. Finally, the protocol could be coupled up to a
disilane-mediated reduction of CO2 to carbon monoxide for the direct incorporation into the target
compound[1].
[1] K. Domino, C. Veryser, T. Skrydstrup et al., Angew. Chem. Int. Ed. 2018, 57, 6858-6862.
STUDENT TALK 7
THE YET UNIDENTIFIED DS2 BINDING SITE – AN UPDATE REPORT
1Frederik Rostrup, supervised by
1Bente Frølund.
1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of
Copenhagen
Universitetsparken 2, DK-2100 Copenhagen, Denmark. [email protected].
Few compounds target the δ-subunit containing GABAA-receptors selectively.
δ-Selective compound 2 (DS2, Figure 1) exhibits functional selectivity towards this subtype of
receptors relative to its action on the -subunit containing receptors.
The binding site of DS2 and its analogues remains undiscovered. Herein we present our efforts to
reveal this binding site and to further explore the SAR.
Figure 1. A synthetic pathway towards DS2 analogues.
The compounds were synthesized via GBB multicomponent reactions(1) and further modified by
Suzuki-Miyaura cross-couplings(2), deprotections(3) and subsequently transformed into amides(4).
Additionally, bioisosteres of the amide were synthesized via different synthetic pathways
(Synthesis will be reported in presentation).
To date, 10 novel compounds have been characterized at a stable cell line in a fluorescence-based
FLIPR membrane potential assay on the α4β1δ (Data not shown). Overall, δ-selectivity was
maintained.
Moreover, a remarkable amount of space was revealed in the R3-position but limited in the R1- and
R2-positions.
Three compounds revealed ago-allosteric pharmacological profile. The structural determinants for
this profile are currently under further investigation.
Moreover, guided by homology modelling, a mutational study was conducted in the α- and the δ-
subunit to affect DS2’s activity in an attempt to pinpoint the binding site. However, DS2 was found
to be active towards all of the δ-mutants and so the binding site remains to be determined.
STUDENT TALK 8
ESTABLISHING CELL PAINTING AT AARHUS UNIVERSITY
Esben B. Svenningsen, Thomas B. Poulsen
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
Cell Painting is an assay to generate morphological profiles based on high-content screening.
Multiplexing 6 fluorophores imaged in 5 channels allows for visualization of 8 cellular components.
Automated image analysis results in 1500 features measured on a per-cell basis, revealing the
phenotype induced by various treatments. This allows for unbiased evaluation of compound
activity.[1]
Using the platform, we have shown that the compound 9-Me SMD, which was reported to not
inhibit protein synthesis, is in fact a protein synthesis inhibitor, by comparing its fingerprint / profile
to similar compounds. This proves the utility of the assay to generate mechanistic insight.
[1] Svenningsen, E. B., Poulsen, T. B., Bioorg. Med. Chem., 2019, doi: 10.1016/j.bmc.2019.03.052
STUDENT TALK 9
SYNTHESIS OF ADENINE AND GUANINE AS ACYCLIC (L)-THREONINOL NUCLEIC ACID
(ATNA) PHOSPHORAMIDITES
Amalie D. Juul, Vipin Kumar, and Kurt V. Gothelf.
Department of Chemistry & Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14,
8000 Aarhus C, Denmark. [email protected]
aTNA is a DNA analogue with a phosphordiester backbone and a peptide bond instead of a sugar unit.
aTNA can bind both DNA and RNA and is able to form G-quadruplexes by Hoogsten hydrogen bonds. This
project follows the synthesis of the nucleobases adenine and guanine as phosphoramidites. The aim of the
project is to investigate triplex formation from antiparallel aTNA purine-hairpins.
USING AROMATIC RINGS AS SOLAR ENERGY BATTERIES
Anders B. Skov, Nicolai Ree, Theis Sølling, Kurt V. Mikkelsen, Mogens Brøndsted Nielsen and Thorsten Hansen.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø. [email protected]
Benzannulated derivatives of the Dihydroazulene-Vinylheptafulvene photoswitch were synthesized and
investigated using femtosecond time-resolved spectroscopy. We show that the energy stored in the
metastable VHF can be tripled by benzannulated, but that aromaticity drastically changes the
photoisomerization dynamics.
A. B. Skov, J. F. Petersen, J. Elm, B. N. Frandsen, M. Santella, M. D. Kilde, H. G. Kjærgaard, K. V. Mikkelsen, M. B. Nielsen,
ChemPhotoChem., 2017, 1, 206-212
POSTER 1
POSTER 2
PH-SENSITIVE NANOBODY DRUG CONJUGATE
Anders Märcher, Kurt V. Gothelf.
INANO, Aarhus University, Gustav Wieds vej 14, Aarhus, Denmark.
A pH-sensitive linker for drug delivery have been synthesized and attached to a tumor targeting nanobody, to
make a nanobody drug conjugate. When the conjugate reaches the tumor it is brought into the cell by
receptor-mediated endocytosis, and the linker is designed to self-immolates in the endosome to release the
drug. The drug and the targeting agent should in principle be interchangeable.
SYNTHESIS OF MOLECULAR ACTUATORS FOR DYNAMIC DNA NANOSTRUCTURES
Angel E. Santorelli Villamizar and Kurt Gothelf.
Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14 (Building 1590), 8000 Aarhus, Denmark.
Azobenzene is known for being capable of reversible cis-trans conversions upon irradiation. Combining
phosphoramidite chemistry and the properties of azobenzene, it is possible to synthesize DNA
oligonucleotides with intercalated azobenzene linkers, capable of changing the oligo structural conformation
and length. These oligoes can be integrated into more complex DNA-origami structures, where light-
activated actuation is potentially achieved on bigger DNA-macromolecules.
POSTER 3
POSTER 4
THIADIAZA[7]HELICENE AND RELATED POLYAROMATIC COMPOUNDS
- Synthesis, properties and applications –
Bodil Lousen and Michael Pittelkow. Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø,
Denmark. E-mail: [email protected]
Polyaromatic compounds are interesting compounds with remarkable properties. On this poster the
synthesis of a family of structurally related compounds, derived from thiadiaza[7]helicene through sequential
oxidations is described. Investigation of photochemical properties, aromaticity and racemization barriers
show that the small structural changes have large effects on the properties of the molecules, both in terms of
fluorescence and the stabilising effect of G-quadruplex DNA.
RECOGNITION OF THIOPHENOLATES WITH BIOTIN[6]URIL HEXAMETHYLESTER
Casper Egholm Jensen and Michael Pittelkow.
Department of chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø, Denmark.
We wish to present biotin[6]uril hexamethylester (B6UOMe) as a novel approach for the recognition of
thiolates in organic solvent. The system was investigated with 1H-NMR, using a set of para-substituted
thiophenolates (p-H, P-NO2, p-OMe and p-COOMe) in d3-acetonitrile. Association constant were measured
with 1H-NMR titrations and showed constants in the range of 65-101 M
-1. It can be concluded that B6UOMe
have applications in thiolate recognition, but the system suffers under low association constants.
1
2
3
4
5
6
POSTER 5
POSTER 6
EXPLOITING PHOSPHATE RECOGNITION TO DRIVE THE DYNAMIC ENZYMATIC
SYNTHESIS OF OLIGOSACCHARIDES
Charlotte Nybro Bjerking and Sophie R. Beeren
Department of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
E-mail: [email protected]
Phosphorylase-catalysed α(1-4)-glucan synthesis can be used to elongate glycosyl acceptors.[1]
However,
elongation is generally disfavoured. Here we investigate using a Dynamic Combinatorial Chemistry (DCC)[2]
approach if the reaction can be driven towards the elongated products by adding a receptor that binds
inorganic phosphate.
[1] O’ Neill, E. C.; Field, R. A., Carbohydr. Res. 2015, 403, 23-37.
[2] Beeren, S. R.; Sanders J. K. M. In Dynamic Combinatorial Chemistry; Reek J. N. H., Otto S. Ed.; Wiley-VCH: Weinheim, Germany,
2010, pp. 1-22.
PLEUROMUTILIN CONJUGATE DESIGN AND SYNTHESIS ASSISTED BY PEPTIDYL
TRANSFERASE CENTER COMPUTATIONAL MODELS
Christoffer Vogsen Heidtmann§, Faidra Voukia
§, Stine Hygum Sørensen
§, Louise Nydam Hansen
§, Peter Reinholdt
§,
Jacob Kongsted§, Brian Urlund
§, Janne Kudsk Klitgaard∥ and Poul Nielsen
§.
§Department of Physics, Chemistry and
Pharmacy, and ∥Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M,
Denmark
The antibacterial effect of pleuromutilin conjugates arises from their blockage of the peptidyl transferase
center (PTC) situated in prokaryotic ribosomes. The poster reports the current synthesis of substituted 22-(4-
(benzyl)-1,2,3-triazolo) pleuromutilin conjugates, as well as the ongoing development of a Prime MM-GBSA
and molecular dynamical Amber MM-PBSA model of the PTC destined for the identification and verification
of new conjugates.
POSTER 7
POSTER 8
INVESTIGATING THE USE OF DNA TRIPLEXES FORMED BY REVERSE HOOGSTEEN BASE
PAIRING IN NANOSTRUCTURE FORMATION
Cindy Ng, Vipin Kumar, and Kurt V. Gothelf.
Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14,
8000 Aarhus C, Denmark. [email protected]
Polypurine hairpins stabilized by intramolecular reverse-Hoogsteen bonds can form a triplex structure with a
polypyrimidine sequence by binding to it with Watson-Crick bonds.[1]
Triplex formation of different hairpins
and target sequences has been investigated and shows that longer DNA strands give a clearer triplex
formation. The use of these DNA triplexes in forming nanostructures has yet to be studied.
[1] Coma, S.; Noé, V.; Eritja, R.; Ciudad, C. J. Oligonucleotides 2005, 15, 269-283.
A PEPTIDE RADIOLIGAND FOR MOLECULAR IMAGING OF POSTSYNAPTIC DENSITY
SCAFFOLDING PROTEINS IN THE BRAIN
Eduardo F. A. Fernandes*a, Mikael Palner, Troels E. Jeppesen, Simone L. Bærentzen, Hans M. Maric, Sören Doose,
Andreas Kjær, Andreas Schlosser, Linda M. Haugaard-Kedström, Matthias M. Herth, Kristian Strømgaard. aCenter for
Biopharmaceuticals, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen 2100,
Denmark. *[email protected]
In our work, we describe a high-affinity radioligand targetting the membrane-associated guanylate kinase
(MAGUK) class of PSPs. We first prepared a 18
F labeled probe, obtained with >95% radiochemical purity
and molar activity ranging between 5-10 GBq/µmol. Autoradiography images of rat brain slices displayed a
differential distribution of radiation density (Figure 1). Cortex, hippocampus, cerebellum and caudate-
putamen regions exhibited higher specific binding than in striatum, which correlated well with the known
MAGUK brain distribution. The selectivity profile of our tracer was evaluated by a proteomic analysis of
pulled-down proteins of whole rat brain lysates using the binding epitope of our tracer as bait. We obtained
significant and selective enrichment of the following PSPs: PSD-95, PSD-93, SAP-97, and SAP-102. Finally,
positron emission tomography (PET) images displayed low tracer uptake in the brain and a fast washout
through the kidneys. We envision that this probe is a valuable tool for in vitro brain imaging studies of PSPs
in the brain and for the future development of new and improved PET imaging radioligands.
POSTER 9
POSTER 10
TOWARDS A RESPONSIVE LANTHANIDE COMPLEX FOR ROS SENSING
Elena Del Giorgio, Thomas Just Sørensen
Nano Science Centre and Department of Chemistry, University of Copenhagen,
Universitetsparken 5, 2100 København Ø, Denmark. [email protected]
Reactive Oxygen Species (ROS) play a fundamental role in biological systems. [1]
Reported probes to detect ROS mostly rely on organic dyes to mediate the response, leading to
autofluorescence issues.[1]
Lanthanide complexes represent an exciting alternative that can sidestep these
problems.[2]
Here, a ROS responsive unit inspired by the oxidation of α-Tocopherol is synthesized and
investigated.
[1] Antioxidants & redox signalling, Volume 29, Number 6, 2018
[2] Uversky V.N et al. (eds) Encyclopedia of Metalloproteins. Springer, New York, NY 2013
ESTABLISHING CELL PAINTING AT AARHUS UNIVERSITY
Esben B. Svenningsen, Thomas B. Poulsen
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
Cell Painting is an assay to generate morphological profiles based on high-content screening. Multiplexing 6
fluorophores imaged in 5 channels allows for visualization of 8 cellular components. Automated image
analysis results in 1500 features measured on a per-cell basis, revealing the phenotype induced by various
treatments. This allows for unbiased evaluation of compound activity.[1]
[1] Svenningsen, E. B., Poulsen, T. B., Bioorg. Med. Chem., 2019, doi: 10.1016/j.bmc.2019.03.052
POSTER 12
POSTER 11
UNRAVELLING THE KAT SUBSTRATE SPECIFICITY – L L ’
LENGTH
Giordano Proietti, Yali Wang, Giorgio Rainone and Jasmin Mecinović.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense,
Denmark. [email protected]
Lysine acetylation, an abundant posttranslational modification found on histone tails, is regulated by the histone lysine
acetyltransferases (KATs). Due to their relevance in drug discovery, alongside the poor inhibitory arsenal developed so
far, a better understanding of the chemical basis underlying KAT catalysis is of great biomolecular and medicinal interest.
In this study, a panel of lysine analogues bearing shorter and longer side chains is incorporated into histone peptides.
Substrate specificity is investigated by MALDI-TOF MS enzyme assays. Results reveal that human KATs have an ability
to catalyse acetylation of residues other than natural lysine.
TEMPLATE-DIRECTED ENZIMATIC SYNTHESIS OF ALPHA-GLUCANS
Giorgia Masciotta, Sophie R. Beeren. Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
The goal of this project is to develop a new approach to the synthesis of oligosaccharides that combines
enzymology with non-covalent host-guest interactions by using templates to direct the enzymatic synthesis
of the specific products. The approach is based on Dynamic Covalent Chemistry1 a synthetic methodology
where building blocks react together reversibly under thermodynamic control in order to create a dynamic
mixture of oligomeric products called Dynamic Covalent Library.
[1] Beeren, S. R.; Sanders J. K. M. In Dynamic Combinatorial Chemistry; Reek J. N. H., Otto S. Ed.; Wiley-VCH: Weinheim, Germany,
2010, pp. 1-22.
POSTER 13
POSTER 14
SOLUTION STATE STRUCTURE OF AMIDE APPENDED LNDO3A COMPLEXES WITH SLOW
AMIDE BOND ROTATION
Helene Obel Bøch Andersena, Alan M. Kenwright
b, and Thomas Just Sørensen
a.
aNano-Science Center & Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø,
Denmark. [email protected].
bDepartment of Chemistry, University of Durham, South Road, Durham, DH1 3LE, U.K.
Kinetically stable DO3A type lanthanide(III) complexes are of great interest due to their applications in
bioimaging and as MRI constrast agents.[1]
To investigate the inherent chirality of the DO3A ligand we have
introduced a chiral amide arm which resolves the many conformations of the complex and illustrates the
complicated speciation that must be taken into account when even simple DOTA-like complexes are used in
an inherently diastereotopic biological medium.
[1] P. Caravan, J. J. Ellison, T. J. McMurry, R. B. Lauffer, Chemical Reviews, 1999, 99, 2293-2352.
SELECTIVE ORGANOCATALYTIC BIOCONJUGATIONS
Henriette Natorp Tobiesen, Karl Anker Jørgensen (Supervisor AU), Søren Bertelsen (Supervisor NN)
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
Research Chemistry 2, Novo Nordisk Måløv, Denmark.
[email protected], [email protected]
Bioconjugation is a valuable tool for making chemical modifications to peptides and proteins to improve their
pharmacodynamics properties. As current methods are rarely fully site- or stereoselective, thereby producing
isomers of products, there is an interest for highly selective bioconjugation methods in the pursuit of new and
high quality pharmaceuticals.
Organocatalysis is a valuable process for making stereoenriched molecules, as it allows you to control
reactivity in three dimensions with the use of small organic molecules. Recently, we proposed a new
reactivity to account for the enantioselective coupling of carboxylic acids to α-branched aldehydes by
combining primary amine catalysis and an oxidant. We are now further exploring this new reactivity, with the
aim of selectively utilizing reactive functionalities in peptides and proteins for new, stereoselective
bioconjugation methods.
POSTER 15
POSTER 16
HANDLING OF CO MADE EASIER: COTABS
Hugo Paul Collin, Marcelo Siqueira Valle, Troels Skrydstrup
iNANO, Aarhus University, Gustav Wieds Vej 14, Aarhus, Denmark.
A new methodology for the safe and fast release of CO
has been developed using bench stable and easy to make
COtabs. The yields of this new methodology (Pill) are
comparable to the reactions made inside the glovebox1
(GB). We also conducted 13
C labelling and a gram scale
reaction. With this advance CO chemistry has been made
more easily accessible to all labs.
[1] Friis, S., Lindhart, A., Skrydstrup, T., Acc. Chem. Res., 2016, 49 (4),
594 – 605.
A SURPRISING LIGAND EFFECT IN THE ELECTROCATALYTIC REDUCTION OF CARBON
DIOXIDE WITH MANGANESE-BIPYRIDINE COMPLEXES
Magnus Rønne, Monica Madsen, Joakim Bøgelund Jakobsen, Kim Daasbjerg, and Troels Skrydstrup
Carbon Dioxide Activation Center (CADIAC), Department of Chemistry and the Interdisciplinary Nanoscience Center
(iNANO), Aarhus University, Gustav Wieds vej 14, 8000 Aarhus C (Denmark).
In a recent study on ortho-functionalized Mn-bypridine complexes, most surprisingly the electrochemical
reduction of CO2 with complexes containing the dialkylamine (e.g. R = NEt2) on the appendages generated
formic acid rather than the expected carbon monoxide obtained for the structurally similar Mn complexes (R
= Me or OH).
CO2, iPrOH or TFE
-1.7 to -2.1 V vs Fc+/Fc
R = OH
TOF ≈ 600 s-1
FE ≈ 90 %
CO2, iPrOH or TFE
-1.7 to -2.1 V vs Fc+/Fc
R = NEt2
TOF ≈ 5000 s-1
FE ≈ 90 %
HCOOHCON N
RR
Mn
Br
COCOOC
POSTER 7
POSTER 18
EVALUATING TRIMETHYLTHIALYSINE AS AN EASILY ACCESSIBLE MIMIC FOR
TRIMETHYLLYSINE TO STUDY EPIGENETIC PROCESSES
Jordi C. J. Hintzen, Bas J. G. E. Pieters, Abbas H. K. Al Temimi and Jasmin Mecinović.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense,
Denmark. [email protected]
To gain a better fundamental understanding of the biomolecular recognition of posttranslationally modified
histones in epigenetics, easily accessible mimics of posttranslationally modified residues can be of great
value. Here we present a study to establish the viability of trimethylthialysine as a mimic for trimethyllysine
through both synthetic chemistry and molecular modelling.1 Easily accessible through cysteine alkylation, we
also present a variety of analogs to further investigate the binding of epigenetic reader proteins.2
A DOUBLE-HEADED NUCLEOTIDE WITH TWO CYTOSINE NUCLEOBASES
Kasper Petersen Beck, Charlotte Reslow-Jacobsen, Mick Hornum and Poul Nielsen.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M,
Denmark. [email protected]
Double-headed nucleotides are capable of condensing the genetic information of DNA.[1]
In this study, a new
double-headed nucleotide with two cytosine bases (CC) was synthesized and incorporated into
oligonucleotides in order to evaluate its effect on the stability of the resulting DNA duplex. For single
incorporations, a considerable thermal stabilization of 4.0 °C was found. It was also shown that CC behaves
as a compressed dinucleotide.[2]
[1] P. Kumar, P. K. Sharma, P. Nielsen, J. Org. Chem., 2014, 79, 11534. [2] K. Beck, C. Reslow-Jacobsen, M. Hornum, C. Henriksen, P. Nielsen, Bioorg. Med. Chem. Lett., 2019, 29, 740.
[1] Jordi C. J. Hintzen, Jordi Poater, Kiran Kumar,
Abbas H. K. Al Temimi, Bas J. G. E. Pieters, Robert S.
Paton, F. Matthias Bickelhaupt, Jasmin Mecinović,
Manuscript submitted
[2] Bas J. G. E. Pieters, Jordi C. J. Hintzen, Yvonne
Grobben, Abbas H. K. Al Temimi, Jos J. A. G. Kamps,
Jasmin Mecinović, Bioconjugate Chem., 2019, 30, 952-
958.
POSTER 19
POSTER 20
DISULFIDE DNA BACKBONE
Kassem El Chami, Kurt Gothelf.
iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
The aim of this project is to synthesize the molecule indicated below which will be utilized in the formation of
a novel DNA backbone comprising disulfide bonds. The molecule is constructed so that it is symmetrical and
contains two methanethiols, a nucleobase, and a carboxylic acid to provide better solubility. A 3’- and 5’-
modified dithiol oligonucleotide will be used as a template for the base pairing of the nucleobase attached to
the dithiol monomer with the oligonucleotide. Base pairing succeeded by oxidation will result in the formation
of the disulfide backbone.
SYNTHESIS OF IMINES AND TERTIARY AMINES BY DEHYDROGENATION OF ALCOHOLS
USING PORPHYRIN COMPLEXES
Kobra Azizi, Sedigheh Akrami and Robert Madsen*
Department of Chemistry, Technical University of Denmark
Manganese(III) porphyrin chloride complexes have been developed for the first time as catalysts for the
acceptorless dehydrogenative coupling of alcohols and amines. The reaction has been applied to the direct
synthesis of imines and tertiary amines where only hydrogen gas and/or water are formed as the
byproduct(s).
[1] K. Azizi S. Akrami, R. Madsen, Chem. Eur. J. 2019, 25,1–9.
POSTER 21
POSTER 22
DYNAMIC STRUCTURES OF LANTHANIDE COMPLEXES IN SOLUTION
Lea Gundorff Nielsen and Thomas Just Sørensen. Nano-Science Center & Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø,
Denmark. [email protected]
a lanthanide(III) ion show a complicated set of dynamic processes in solution.[1] Here, the dynamic exchange process between two sets of enantiomeric forms have been investigated by paramagnetic 1H-NMR and lanthanide centred luminescence. The results clearly show that the structure of the ligands is the critical parameter for control and design of structural flexibility. As the possible conformations in solution determine the properties of lanthanide based MRI contrast agents, structural control is critical.
[1] Parker, D. et al., Chemical Reviews 2002, 102 (6), 1977-2010
SYNTHESIS AND CHARACTERIZATION OF GPR15 RECEPTOR PEPTIDE ANALOGS
Lieke van Gijzel, Claudia Perez, Line Vedel, Partick Gentry, Bengt H. Gless,
Christian A. Olsen, David E. Gloriam, Hans Bräuner-Osborne, Trond Ulven
Department of Drug Design and Pharmacology, Faculty of Health and Medical Science, University of Copenhagen,
Universitetsparken 2, Copenhagen, 2100, Denmark
The GPR15 is expressed in the colon and lymphocytes in the human body, where it can be used as a co-
receptor of the simian immunodeficiency virus and HIV-2 by trafficking T-cells to the lamina propria1. Potent
agonists and antagonists are therefore of interest as research tools and drug discovery leads. Recently, the
peptide GPR15L was identified as an endogenous ligand of GPR151. Being a 57 residue peptide, GPR15L
is not suitable as lead for small-molecule drug discovery. Shorter C-terminal fragments of GPR15L have also
been found active on the receptor2. The goal of this project is to synthesize these short isoforms and to
systematically introduce variations to elucidate sequence-activity relationships. The data can then be used
for computational modelling to obtain novel peptide mutants with a higher binding potency for the GPR15.
The identification of novel smaller peptide ligands for the GPR15, which contain a higher binding affinity for
the receptor, can be interesting as a tool for further exploration of GPR15 and potentially as drug discovery
leads.
[1] Suply, T.; Hannedouche, S.; Carte, N.; Li, J.; Grosshans, B.; Schaefer, M.; Raad, L.; Beck, V.; Vidal, S.; Hiou-Feige, A.; et al. A Natural Ligand for the Orphan Receptor GPR15 Modulates Lymphocyte Recruitment to Epithelia. Sci. Signal. 2017, 10 (496), eaal0180. https://doi.org/10.1126/scisignal.aal0180. [2] Ocón, B.; Pan, J.; Dinh, T. T.; Chen, W.; Ballet, R.; Bscheider, M.; Habtezion, A.; Tu, H.; Zabel, B. A.; Butcher, E. C. A Mucosal and Cutaneous Chemokine Ligand for the Lymphocyte Chemoattractant Receptor GPR15. Front. Immunol. 2017, 8, 1111. https://doi.org/10.3389/fimmu.2017.01111
POSTER 23
POSTER 24
DTFS AND EXTENDED TTFS – ELECTRONIC APPLICATIONS IN FUNCTIONAL MATERIALS
Line Broløs, Josefine Mogensen, Dianna Andersen and Mogens Brøndsted Nielsen.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark.
Tetrathiafulvalene (TTF) is a widely used molecular entity in supramolecular chemistry and functional
materials, due to unique redox properties. Extended TTFs pose as interesting candidates when developing
new functional materials with low oxidation potentials and favorable intermolecular interactions.1 In these
projects dithiafulvene (DTF) and extended TTF have been employed with several purposes in mind - all
exploiting the good donating properties and low oxidation potentials of these structural units.
[1] J. Rybácek, M. Rybácková, M. Høj, M. Belohradský, P. Holý, K. Kilsa and M. B. Nielsen, Tetrahedron 2007, 63, 8840-8854.
FOLDAMER-PEPTIDE INTERACTION
Line M. Langhorn, Joseph M. Rogers, Céline Douat, Hiroaki Suga, Michael Pittelkow, and Ivan Huc
Department of Pharmacy, Ludwig-Maximailians-Universität, Butenandtstraße 5-13, D-81377 Munich, Germany.
A foldamer was developed and synthesized and through Random nonstandard Peptide Integrated Discovery
(RaPID) experiments a sequence of peptides were elected to bind to the foldamer. Two modified quinoline-
based 12-foldamers have afterwards been synthesized, each designed with two different tyrosine-like
monomer-sidechains. One of the elected peptide-strands has been resynthesized and will be used to
investigate the foldamer-peptide interactions.
POSTER 25
POSTER 26
DOUBLE-HEADED NUCLEOTIDES WITH TRIAZOLE AND ETHYNYL LINKERS
Linette Ruder, Sascha H. Carlsen, Henriette B. Christensen, Nikolaj A. Risgaard, Michael Petersen, and Poul Nielsen.*
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense,
Denmark. [email protected]
Double-headed nucleotides have shown to work as compressed dinucleotides condensing the information in
DNA.1 Two new double-headed nucleotides have been synthesized using Sonogashira and CuAAC-
reactions. Molecular dynamics simulations indicate promising recognition properties when incorporated into
DNA.
[1] M. Hornum, J. Stendevad, P. K. Sharma, P. Kumar, R. B. Nielsen, M. Petersen and P. Nielsen, Chem. Eur. J., 2019, in press.
ACETYLENIC SCAFFOLDING OF SUBPHTHALOCYANINES
Mads Georg Rasmussen, Mogens Brøndsted Nielsen
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark.
The Subphthalocyanine chromophore is a dye of interest for light harvesting, as it has already shown to
perform in devices.[1]
Here we present the synthetic work of macromolecular structures of the
Subphtalocyanine dye towards donor-acceptor based light harvesting systems.
[1] M. Grätzel, J. Photochem. Photobiol. C Photochem. Rev. 2003, 4, 145–153.
POSTER 27
POSTER 28
ACYCLIC THREONINOL NUCLEIC ACID - ATNA
Mads K. Skaanning and Kurt V. Gothelf.
iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark. [email protected]
During the last decade, the interest in artificial nucleic acids has intensively increased due to their potential
therapeutic application such as control of gene expression. One of these artificial nucleic acids is (L)-acyclic
threoninol nucleic acid (aTNA), which has showed the ability to form highly stable triplex structures with
homopurine DNA and RNA strands. The goal of this project is to synthesize new aTNA nucleobases and test
their ability to form triplex structures with DNA containing thymine and cytosine nucleobases.
SOLID PHASE DIRECTED SYNTHESIS OF CONJUGATED OLIGOMERS
Maja E. T. Langballe, Rikke Hansen, Mikael Madsen, and Kurt V. Gothelf.
iNANO, Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
The aim of this project is to control the sequence of conjugated oligomers using solid phase directed
synthesis. This is achieved by synthesizing monomers as phosphoramidites and incorporating these into a
DNA strand by solid phase DNA synthesis. The monomers are aromatic molecules with alkene groups,
which make it possible to couple the monomers by olefin metathesis, after they have been incorporated into
the DNA strand.
POSTER 29
POSTER 30
Discovery of pH-sensing human antibodies against different classes of animal toxins
Manuela B. Pucca1,2
, José E. Barbosa3, Felipe A. Cerni
1,3, Isadora S. de Oliveira
4, Karla de C. F. Bordon
4, Eliane C.
Arantes4, Andreas H. Laustsen
1
In comparison to conventional antibodies, antibodies with pH-dependent target binding properties can be designed to readily bind antigens at neutral pH, but dissociate from these antigens once the antibody-antigen complexes are internalized by endocytosis into the acidic late endosomes. This allows the antigen-free antibodies to be recycled back to the cell surface, mediated by the neonatal Fc receptor (FcRn), while the dissociated antigens are trafficked to the lysosomes for degradation. By repeating this cycle of antigen binding in plasma and dissociating in the late endosomes, the half-life of pH-dependent antibodies is extended, leading to greater antigen clearance per antibody molecule. In turn, this may enable the use of lower therapeutic dosages. Following phage display selections using pH-engineered elution steps, phages presenting high affinity pH-dependent antibodies targeting different classes of toxins were discovered. These toxins include melittin (a lytic factor from Africanized bee venom), Ts1 (a neurotoxin from Tityus serrulatus scorpion venom), and basic crotoxin (a phospholipase A2 from Crotalus durissus collilineatus snake venom). The results presented here represent the first report on the exploration of pH-dependent antigen binding in the field of toxin neutralization and may enable the application of novel therapeutic strategies for treating animal envenomings.
COPPER CATALYSED AND ADDITIVE FREE DECARBOXYLATIVE
TRIFLUOROMETHYLATION OF (HETERO)AROMATIC IODIDES
Martin B. Johansena and Anders T. Lindhardt
a,b
aDepartment of Engineering and The Interdisciplinary Nanoscience Center (iNANO), Carbon Dioxide Activation Center
(CADIAC), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark. bTeknologisk Institut, Life Science Division, Kongsvang Allé 29, 8000 Aarhus C, Denmark.
The trifluoromethyl group is an important functionality that can be found in many pharmaceuticals and
agrochemicals, being strategically installed to fine-tune metabolic and chemical properties of these bioactive
molecules. However, the incorporation of the trifluoromethyl group in aromatic compounds is often costly in
fluorinating agents or requires the use of (super)stoichiometric transition metals.
In this work, we have developed a copper catalysed decarboxylative trifluoromethylation of (hetero)aromatic
iodides operating in the absence of ligands and specialized additives. The protocol takes advantage of
copper(I) oxide, being an atom economical, cost effective and readily available copper source, in the
presence of potassium trifluoroacetate. The reaction could successfully be scaled up from 0.5 mmol to 15
mmol, also resulting in an increased isolated yield. Finally, late-stage installation of the trifluoromethyl
functionality afforded the N-trifluoroacetamide variant of the antidepressant agent, Prozac, demonstrating the
applicability of the developed protocol.
POSTER 31
POSTER 32
SMALL CYCLIC OLIGONUCLEOTIDES
Martin Frandsen, Alexander Frederik Sandahl, and Kurt V. Gothelf.
iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
The poster will present the synthesis of a thymidine base analog and its subsequent use in making small
cyclic oligonucleotides. The synthesis is a linear seven step synthesis starting from 5-methyluridine followed
by coupling to a PEGA resin. Previous known issues with 2’-3’ migration was resolved, and no migration was
observed. On the solid support short oligonucleotides were synthesized and it was attempted to make cyclic
oligonucleotides but due to unknown issues no cyclic oligonucleotides could be formed.
UMPOLUNG MEDIATED CARBOXYLATION OF ALDEHYDES
Martin Juhl, Ji-Woong Lee.
Department of Chemistry, Copenhagen University, Universitetsparken 5, 2100 København Ø, Denmark.
A mild and direct carboxylation reaction of aldehydes using CO2 is presented. An umpolung strategy was
employed and through mechanistic investigations a detailed understanding of the reaction was achieved.
Furthermore, the α-keto acid product proved to be a valuable substrate in the synthesis of amino acids.
[1] M. Juhl, J.-W. Lee. Angew. Chem. Int. Ed. 2018, 57, 12318.
[2] M. Juhl, M. J. Kim, H.-Y. Lee, M.-H. Baik, J.-W. Lee. Synlett. 2019, 30, A-J
POSTER 33
POSTER 34
INVESTIGATION OF THE CHROMIUM(III) SALEN-CATALYZED DEHYDROGENATION OF
ALCOHOLS
Maryam Pirouz, Robert Madsen.
Chemistry department, Technical university of Denmark, lyngby, Denmark.
The first example of a chromium (III) catalyst for the acceptorless dehydrogenation of alcohols is presented.
N,N-Bis(salicylidene)-1,2-cyclohexanediaminomanganese(III) chloride has been shown to catalyze the direct
synthesis of imines from a variety of alcohols and amines with the liberation of hydrogen gas.
Dehydrogenation of the alcohol takes place by a hydrogen transfer generating a chromium(III) salan hydride
from which hydrogen gas is released.
AFFINITY-BASED PROBES TO INVESTIGATE POST-TRANSLATIONAL MODIFICATIONS
Michael Bæk, Ahmed Embaby, Pablo Martin-Gago, Jonas S. Laursen, Julie L. H. Madsen, and Christian Adam Olsen*
Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark.
Recently, enzymes thought to be protein lysine deacetylases, have been shown to target different types of
acyl modifications on lysine residues, including crotonyl, glutaryl, and myristoyl.1 In order to investigate the
hypothesis that, yet unknown, proteins of biochemical importance may recognize these post-translational
modifications, we have developed a novel set of affinity-based probes (AfBPPs).
Figure 2. AfBPP design based on histone 3 with Lys-9 modified.
Because such ABPs are aimed at investigating enzymes that recognize or cleave these modifications, they
are potential substrates for the target enzymes.2,3
This will cause the probes to be degraded when
performing assays using active enzymes, thus providing unambiguous results. In order to circumvent this
cleavage, we introduce thioamide and hydrazide motifs as acyl group analogs. These motifs are known to
inhibit NAD+-dependent deacylase enzymes (sirtuins).
2,3 We envision that these motifs will improve the
structural integrity of our probes in cellular environments.
1. Bheda, P., Jing, H., Wolberger, C. & Lin, H., Annu. Rev. Biochem. 85, 405–29 (2016). 2. Dancy, B. C. R. et al., J. Am. Chem. Soc. 134, 5138–5148 (2012). 3. Fatkins, D. G., Monnot, A. D. & Zheng, W., Bioorg. Med. Chem. Lett. 16, 3651–3656 (2006).
ALPKNH
TG
O
Y
HN
PTM
X
NH
PQ
O
NN
NH2
O
PTM: Ac, Myr, Glut, CrX: CH2 or NHY: O or S
POSTER 35
POSTER 36
SELF-PROMOTED AND STEREOSELECTIVE N-GLYCOSYLATION
Michael M. Nielsen, Patrycja Mała, Eirikur Þ. Baldursson and Christian M. Pedersen.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen O, Denmark.
A stereoselective and self-promoted synthesis of β-N-glycosyl sulfonamides that requires no catalysts or
additives is presented. The acidic sulfonyl carbamates are obtained in one step and can be condensed with
an α-TCA electrophile, facilitating the formation of the desired products. With 40 examples and yields of
<95%, this is an appealing strategy for the synthesis of various N-glycosides and glycopeptides.
DESIGN, SYNTHESIS AND EVALUATION OF SELECTIVE GALECTIN-8 INHIBITORS
Mujtaba Hassan, Floriane Baussière, Ulf J. Nilsson. Centre for Analysis and Synthesis, Lund University, Naturvetarvägen 14/Sölvegatan 39 A, Lund, Sweden.
Galectins are a family of carbohydrate-binding proteins that modulate the cellular mechanisms, the immune system, tumour growth, and metastasis, thus they represent promising targets for drug discovery and development. Galectin-8 plays a key role in autophagy and pathologic lymphangiogenesis, which is implicated in tumour growth, solid organ graft rejection, corneal inflammations, and type 2 diabetes. Based on the previously published qunionline-galactopyranoside hybrid that represents the most selective galectin-8 inhibitor hitherto,1 a library of C-3 substituted galactopyranoside derivatives bearing fused bicyclic heterocycles was designed and synthesized. The galactopyranoside derivatives were evaluated as inhibitors of galectin-3 and 8N in a competitive fluorescence polarization assay. The study revealed that galactopyranoside derivative bearing benzimidazole ring possesses comparable binding affinity for galectin-8N as the lead compound and superior selectivity against galectin-3. The compound represents a better lead compound, as it has lower cLogP and provides a room for further functionalization as opposed to quinoline.
POSTER 37
POSTER 38
IMIDAZOLE CARBAMATE PROBES FOR AFFINITY GUIDED AZIDE-TRANSFER TO METAL-
BINDING PROTEINS
Nielsen N. L., Mortensen M. R., Palmfeldt J. and Gothelf K. V.
Department of Chemistry, iNANO center, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
By using imidazole carbamate probes for affinity guided labeling of metal binding proteins, we are able to
transfer an azide handle to a wide variety of proteins, including antibodies, enzymes, nanobodies and His6-
tagged proteins. The synthesis of two probes are demonstrated, and comparison showed that the probe
containing three NTA groups provided higher selectivity than the probe containing two.
[1] Mortensen M. R., Nielsen N. L., Palmfeldt J., Gothelf K. V., Org. Biomol. Chem. 2019, 17, 1379–1383.
ORGANOCATALYTIC [10+4] CYCLOADDITIONS
Nicolaj Inunnguaq Jessen, [email protected]
Supervisor: Karl Anker Jørgensen
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
Higher-order cycloadditions constitute a potent tool in the construction of cyclic scaffolds in organic
chemistry. The use of polyconjugated systems typically entail periselectivity challenges. Furthermore,
stereoselectivity is important in the formation of stereogenic centers. Two types of catalytic [10+4]
cycloadditions have been reported, one yielding tetracyclic products in excellent enantio- and
diastereoselectivities and one yielding aromatic benzo[a]azulenes.
POSTER 39
POSTER 40
COMPARING COMMON APPROACHES FOR WATER SOLUBILITY THROUGH THE
PHOTOPHYSICAL PROPERTIES OF THE LONG LIFETIME FLUOROPHORE DAOTA+
Niels Bisballe and Bo W. Laursen.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø, Denmark.
Organic chromophores are hydrophobic in nature, but good solvation in aqueous medium is required for
many applications in biological sciences. The long fluorescence lifetime chromophore DAOTA+ was made
water soluble through the introduction of cationic and zwitterionic side chains (1 and 2), bringing its
photophysical properties in water on par with the parent chromophore (3) in acetonitrile1.
[1] Bogh S. A. et al., ACS Omega, 2017, 2, 193-203.
SYNTHESIS AND OPTICAL PROPERTIES OF PH DEPENDENT [5] AND [6]HELICENES
Nina Gravesen Salinas and Bo W. Laursen.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark.
Helicenes are helical polyaromatic compounds that have attracted significant attention due to their helical
chirality and electronic properties. [1]
Starting from the commercially available 2,6-Dimethoxybenzoic acid the
below presented [5] and [6]Helicenium ions were obtained with a 5 and 6 step synthetic route. The helicenes
hold strong fluorescent properties which are dependent on pH making them very interesting targets for future
applications.
[1] Y. Shen and C. Chen, Chemical Reviews., 2012, 112, 1463-1535.
POSTER 41
POSTER 42
NON-METAL CATALYZED C-C BOND FORMATION OF ALUMINIUM-ALKOXIDE
INTERMEDIATES WITH ARYL BORONIC ACIDS
Oliver Raae Gedde
Carbon Dioxide Activation Center (CADIAC), Department of Chemistry and the Interdisciplinary Nanoscience Center
(iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark), [email protected]
Non-metal catalyzed C-C bond forming reactions are receiving more attention in the development of
sustainable synthetic chemistry.[1]
In this work, we report a new protocol for the coupling of benzylic alcohols,
ketones, and aldehydes with aryl boronic acids, yielding the corresponding 1,1-diarylalkanes. The key step in
this transformation is the formation of the aluminium-alkoxide intermediate, representing the active coupling
partner. After the formation of this intermediate, coupling with the aryl boronic acid partner is performed at
110 oC for 16 hours.
[1] J. Barluenga, M. T. Gamasa, F. Aznar, C. Valdés, Nature Chemistry, 2009, 1, 494-499.
DNA FUNCTIONALIZED CONJUGATED POLYMERS
Rikke A. Hansen, Mikael Madsen, Kurt V. Gothelf.
iNANO, Århus University, Gustav Wieds Vej 14, 8000 Århus, Denmark.
Organic conjugated polymers are intriguing molecules with a wide variety of applications. The development
of DNA-graftet conjugated polymers has allowed high conformational control as well as single molecule-
studies. The aim of this project is to synthesize conjugated polymers functionalized with orthogonal DNA
strands to allow even higher control and manipulation on nanoscale.
POSTER 43
POSTER 44
SMALL SCALE HYDROFORMYLATION USING SOLID PRECURSORS FOR SYNGAS
GENERATION IN A TWO-CHAMBER SETUP
Samuel Kjærsgaard Pedersen, Anja Thomassen, Hans Christian Dahl Hammershøj, Bjarke Skyum Donslund, Dennis
Ulsøe Nielsen, Troels Skrydstrup. Department of Chemistry and iNANO, Aarhus University, Gustav Wieds Vej 14, 8000
Aarhus C, Denmark, [email protected]
Herein, we present a new protocol that enables the Rh-
catalyzed hydroformylation of terminal alkenes on
scales of approx. 0.5 mmol of the olefin. Ex situ
generation of CO and H2 allows for easy 13
C and D
labeling of the products.
[1] S. D. Friis, R. H. Taaning, A. T. Lindhardt, T. Skrydstrup, J. Am. Chem. Soc. 2011, 133, 18114–18117
[2] M. Flinker, H. Yin, R. W. Juhl, E. Z. Eikeland, J. Overgaard, D. U. Nielsen, T. Skrydstrup, Angew. Chem. 2017, 56, 15910 –15915
SITE-SPECIFIC PHOSPHORYLATION OF SYNTENIN USING SEMISYNTHESIS, FOR THE
STUDY OF PROTEIN-PROTEIN INTERACTIONS IN CANCER PROGRESSION PATHWAYS
Ma, S., Clemmensen, L., Özcelik, D., Strømgaard, K. Center for Biopharmaceuticals, Department of Drug Design and Pharmacology, University of
Copenhagen, Copenhagen, Denmark [email protected]
Syntenin is an intracellular scaffolding protein that has gained increasing attention for its role in the
progression of various forms of cancer cells, namely in melanoma, breast, and gastric cancers.1-2
This
adapter protein participates with membrane proteins in a broad range of intracellular protein-protein
interactions (PPIs) through its PDZ domains3-6
, modulating cell-cell communication7, cell proliferation and
membrane forming pathways.1 Previous work with phosphomimetics found that syntenin-mediated pathways
are regulated by phosphorylation and homodimerization.8-10
Certain sites also act as phosphoswitches that
deactivate syntenin autoinhibition.11
Moreover, mass spectrometry identified new phosphorylation sites12
that
require further study to identify their function, associated kinases, and other mechanistic details. Therefore,
our overall goal is to conduct a comprehensive study on how specific phosphorylation sites in syntenin
contribute to its regulation. We developed a semisynthetic strategy to generate syntenin with site-specific
phosphorylations in the disordered N-terminal region upstream of the PDZ domains, using expressed protein
ligation (EPL). We then employed these phosphorylated variants in biophysical assays to discern the effects
of phosphorylation on protein structure, oligomerization states, and binding affinities with known interaction
partners. These endeavors, combined with our group’s previous efforts in the development of syntenin
inhibitors, will enable us to understand how these networks can be exploited as new therapeutic targets, in
particular for cancer.
Acknowledgements The project receives funding from: - The European Union´s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No: 675341; - Agnes og Poul Friis Fond
POSTER 45
POSTER 46
DISCOVERY OF HUMAN MONOCLONAL ANTIBODIES AGAINST CYTOTOXINS FROM THE
FOREST COBRA (Naja melanoleuca) VENOM
Shirin Ahmadi1,2
, Andreas B. Bertelsen1, Andreas H. Laustsen
1
[email protected] 1Department of Biotechnology and Biomedicine, Technical University of Denmark, Denmark
2Department of Biotechnology and Biosafety, Eskisehir Osmangazi University, Turkey
Each year, over 100,000 deaths and many more amputations are caused by venomous snakes, with the
majority of accidents occurring in rural parts of the tropics1. Currently, the only specific treatment against
snakebite envenoming is the use of polyclonal antibodies derived from the plasma of hyperimmunized
animals2. Despite being effective, these antivenoms have different drawbacks, including batch-to-batch
variation in their manufacture and a propensity to cause adverse reaction due to their heterologous nature.
Therefore, there is an urgent need for safer and more efficacious antivenoms against snakebite envenoming.
Human monoclonal antibodies are considered one of the most promising therapeutic modalities for a new
generation of antivenoms, as these have low immunogenicity and can be produced by recombinant
expression. In this study, using phage display technology, human monoclonal scFv fragments against venom
fraction 16 of the forest cobra (Naja melanoleuca) were discovered and their toxin-binding ability was
assessed by ELISA. Our results show that human antibody fragments may find utility in the development of
novel treatments against envenoming caused by the forest cobra, which is one of the most dangerous
African snakes.
[1] Gutiérrez, J.M., Williams, D., Fan, H.W. and Warrell, D.A., 2010.Toxicon, 56(7), pp.1223-1235 [2] Laustsen, A.H., Engmark, M., Milbo, C., Johannesen, J., Lomonte, B., Maria Gutierrez, J. and Lohse, B., 2016. Current Pharmaceutical Design, 22(34), pp.5270-5293
NICKEL-MEDIATED CARBON ISOTOPE EXCHANGE THROUGH DECARBOXYLATIVE
CARBONYLATION OF REDOX-ACTIVE ESTERS
Simon S. Pedersena, Oskar Bakkeholm
a, Liselotte Karulf
a and Troels Skrydstrup
a
a) Carbon Dioxide Activation Center (CADIAC), Department of Chemistry and the Interdisciplinary Nanoscience Center
(iNANO), Aarhus University (Denmark).
The development of a carbon isotope exchange reaction, which is able to fully incorporate labelled carbon
through a nickel-mediated decarboxylative carbonylation of redox-active esters, is presented. The reaction
employs a non-innocent pincer ligand that is proposed to capture the labelled intermediate through reductive
elimination, afterwhich subsequent hydrolysis renders the product and the ligand. The method could be a
valuable tool for the late-stage incorporation of carbon isotopes into carboxylic acids for the required ADME
studies of drug candidates [1].
[1] A. A. Corresponding Author, B.B. Nextauthor, C. Author, J. of Amaz. Chem., 2016, 16, 25-27.
POSTER 47
POSTER 48
DEVELOPMENT AND MECHANISTIC INVESTIGATION OF THE MANGANESE(III) SALEN-
CATALYZED DEHYDROGENATION OF ALCOHOLS[1]
Simone V. Samuelsen,1
Carola Santilli,1 Mårten S. G. Ahlquist,
2 and Robert Madsen*
1Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
2KTH Royale Institute of Technology, 10691 Stockholm, Sweden
Email: [email protected]
Herein, we present the first example of a manganese(III) catalyst for the acceptorless dehydrogenation of
alcohols. N,N’-Bis(salicylidene)-1,2-cyclohexanediaminomanganese(III) chloride has been shown to catalyze
the dehydrogenation of alcohols with the liberation of hydrogen gas. The complex has been used to catalyze
the direct synthesis of imines from a variety of alcohols and amines [1].
[1] S. V. Samuelsen, C. Santilli, M. S. G. Ahlquist, R. Madsen, Chem. Sci., 2019, 10, 1150-1157.
DNA-GRAFTED POLYACRYLATE
Steffen Gasbjerg, Mikael Madsen & Kurt V. Gothelf.
iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
The aim of the project is to synthesize a DNA-grafted polymer using polyacrylic acid for drug delivery and
DNA-origami. The DNA-sidechains will bind the complementary DNA-strands which can be loaded with both
drugs, fluorophores and target directing groups as folic acid, aptamers or antibodies. The flexible backbone
of the grafted-polymer makes it a good candidate for flexible structures on a DNA-origami.
POSTER 49
POSTER 50
CARBON DIOXIDE-CATALYZED STEREOSELECTIVE CYANATION OF COUMARINS
Tamal Roy,1 Myungjo J. Kim,
2,3,‡ Yang Yang,
1,‡ Suyeon Kim,
2,3 Gyumin Kang,
2,3 Xinyi Ren,
1 Anders Kadziola,
1 Hee-Yoon Lee,
2* Mu-
Hyun Baik2,3,
* and Ji-Woong Lee1,
* 1Department of Chemistry, University of Copenhagen, Universitetsparken 5, Copenhagen Ø, 2100, Denmark
2Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea
3Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 34141, Korea
Email: [email protected]
We report a unique and operationally simple carbon dioxide catalyzed cyanation of coumarins followed by
ring-opening/protonation cascade to obtain -cyano carboxylic acid derivatives. Carbon dioxide in
combination with cyanide spontaneously forms cyanoformate and bicarbonate in presence of water which
may be substituted as a convenient cyanide source to avoid the direct use of cyanide.1,2
Surprisingly, we
found under optimized reaction conditions CO2 catalyzed cyanation of a number of 3-substituted coumarins
gave the corresponding -nitrile carbonyls in high chemo- and diastereo- selectivity, whereas poorer
reactivities and selectivities were obtained under argon or nitrogen (scheme 1). The general applicability of
the current process was validated in large scale (5 g) synthesis of
methyl 3-cyano-3-(2-hydroxyphenyl)-2-phenylpropanoate with
chromatography, followed by the synthesis of biologically relevant
heterocyclic compounds. In depth, computation and experimental
analysis were performed to suggest the catalytic role of CO2,
bicarbonate and carbonic acid as Lewis-and Brønsted acids in
activation of the substrate.
[1] L. J. Murphy, K. N. Robertson, S. G. Harroun, C. L. Brosseau, U. Werner-
Zwanziger, J. Moilanen, H. M. Tuononen, J. A. C. Clyburne, Science 2014, 344,
75.
[2] C. Hering, J. von Langermann, A. Schulz, Angew. Chem. Int. Ed. 2014, 53,
8282-8284.
CONFORMATIONALLY SWITCHABLE GLYCOSYL DONORS
Thomas Holmstrøm and Christian Marcus Pedersen. Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø, Denmark.
The reactivity of glycosyl donors is dependent on the conformation of the pyranoside ring.[1]
Glycosyl donors
functionalized with 2,2’-bipyridine moieties on the 3-OH and 6-OH or the 2-OH and 4-OH undergoes a
conformational change forming 1:1 complexes with Zn2+
ions. The reactivities of the two glycosyl donors
were investigated by performing a series of glycosylations in the presence or absence of Zn2+
ions.
[1] Pedersen, C. M.; Nordstrøm, L. U.; Bols, M. J. Am. Chem. Soc. 2007, 129, 9222-9235.
0 20 40 60 80 100 120
0
20
40
60
80
100
Yie
ld (
%)
Time (min)
Under CO2
Under Ar
Scheme 1. Hydrocyanation and ring-opening
reaction of coumarin 1a and a comparison of
reactivities of 1a under CO2 (blue) and argon
(red) as a function of time.
POSTER 51
POSTER 52
SYNTHESIS OF C3 AND C9 SIALIC ACID DERIVATIVES AS LIGANDS TO THE BACTERIAL SODIUM SOLUTE SYMPORTER FROM P. MIRABILIS
T. Bozzola,
a U. Ellervik,
a U. J. Nilsson
a
. aCentre for Analysis and Synthesis, Lund University, Sweden 22100
A recently published bacterial (P. mirabilis) Sodium Solute Symporter (SSS) crystal structure has opened up the way for structure-guided design of sialic acid derivatives as inhibitors.
Here we present the design, synthesis, and evaluation of C-3 and C-9 sialic acid derivatives in order to gain a deeper understanding of the Structure-Activity Relationships in inhibiting the SSS protein. Evaluation of binding to the SSS protein with nano Differential Scanning Fluorimetry (nanoDSF) and Isothermal Titration Calorimetry (ITC) revealed novel compounds that bind with potency almost equal to that of the endogenous substrate, in the low micromolar range.
THERMODYNAMIC STUDIES OF HALOGEN-CARBONYL INTERACTION IN GALECTIN-3
Maria Luisa Verteramo1, Fredrik R. Zetterberg
2, Veronika Chadimová
1 & Ulf J. Nilsson
1
1 Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Lund, Sweden,
2 Galecto Biotech AB, Sahlgrenska Science Park, Gothenburg, Sweden.
A set of galectin inhibitors was designed to investigate the thermodynamic profile of halogen bond
to the carbonyl of G182 in galectin-3C. The thermodynamic fingerprint was measured by
isothermal titration calorimetry (ITC). Results show the congruence between enthalpy and halogen
polarizability, however the iodine derivative has a major entropic penalty, which is reflected in the
KD values received by competitive fluorescence polarization assay. [1]
[1] Verteramo, Maria Luisa, et al. " Structural and Thermodynamic Studies on Halogen-bond Interactions in Ligand–galectin-3
Complexes: Electrostatics, Solvation and Entropy Effects." Manuscript (2019).
POSTER 53
POSTER 54
USING COPILLS FOR PD-CATALYZED CARBONYLATION REACTIONS WITHOUT
GLOVEBOX
Wallace J. Reis*§, Rossimiriam P. Freitas
§, Dennis U. Nielsen*, Troels Skrdstrup*.
*Department of Chemistry, Interdisciplinary Nanoscience Center (iNANO), Carbon Dioxide Activation Center (CADIAC), Aarhus
University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; §Departamento de Química, ICEx, UFMG. Av. Pres. Antônio Carlos, 6627,
Pampulha, Belo Horizonte, MG 31270-901, Brazil.
We reported in 2011 two-chamber system (COware), wich enable safe release CO gas from a
crystalline acid chloride (COgen) an applied on Pd-Catalyzed carbonylations.1 Now, we therefore
mixed COgen, Pd(OAc)2 and HBF4P(tBu)3 that could be pressed into a COtabs, that only require a
stock solution amine to rapid and safe production of CO. Using COpills in three different
carbonylations was showed similar yields compared to literature procedures, without glovebox
system.
1. Hermange, P.; Lindhardt, A. T.; Taaning, R. H.; Bjerglund, K.; Lupp, D.; Skrydstrup, T. J. Am. Chem. Soc. 2011, 133, 6061-6071.
PREGNENOLONE SULFATE ANALOGUES AS NEGATIVE ALLOSTERIC MODULATORS FOR
GABAA RECEPTOR – CHEMISTRY, PHARMACOLOGY & MD SIMULATION
Yue Xu*, Martin Mortensen, Mohamed Shehata, Bente Frølund.
E-mail: [email protected]
GABAA receptors, a series of heteropentameric ligand-gated ion channel, can be activated by the
endogenous inhibitory neurotransmitter GABA followed by internal flow of chloride ion and simultaneous
hyperpolarization to inhibit the excitation of neurons. Neurosteroids can act as either positive allosteric
modulators (PAMs) or negative allosteric modulators (NAMs) for GABAA receptors. The binding sites of
PAMs and NAMs have been identified to be located differently, while both of them are largely exposed to the
lipid membrane. This research focuses on the inhibitory neurosteroids with the aim to investigate SAR of
pregnenolone sulfate by the means of modifying C-21 position and following functionality test on α1β2γ2
GABAA receptor, which suggested the basicity of 21-substituents could have profound influence on the
balance between different states of GABAA receptor, rest, activated and desensitized. Eventually molecular
dynamic simulation was carried out to expose the molecular basis for different modulatory mechanism.
POSTER 55
POSTER 56
Poster No. Name University
P1 Amalie Juul Aarhus University
P2 Anders Märcher Aarhus University
P3 Anders Skov KU - KEMI
P4 Angel E. Santorelli Aarhus University
P5 Bodil Lousen KU - KEMI
P6 Casper Egholm Jensen KU - KEMI
P7 Charlotte Nybro Bjerking DTU
P8 Christoffer Heidtmann SDU
P9 Cindy Ng Aarhus University
P10 Eduardo Felipe Alves Fernandes KU - FARMA
P11 Elena del Giorgio KU - KEMI
P12 Esben Svenningsen Aarhus University
P13 Giordano Proietti SDU
P14 Giorgia Masciotta DTU
P15 Helene Andersen KU-KEMI
P16 Henriette Natorp Tobiesen Aarhus University
P17 Hugo Collin Aarhus University
P18 Joakim Bøgelund Jakobsen Aarhus University
P19 Jordi Hintzen SDU
P20 Kasper Beck SDU
P21 Kassem El-Chami Aarhus University
P22 Kobra Azizi DTU
P23 Lea Nielsen KU - KEMI
P24 Lieke van Gijzel KU-FARMA
P25 Line Langhorn KU - KEMI
P26 Line Mouritsen Broløs KU - KEMI
P27 Linette Ruder SDU
P28 Mads Georg Rasmussen KU - KEMI
P29 Mads Koch Skaanning Aarhus University
P30 Maja E. T. Langballe Aarhus University
P31 Manuela Berto Pucca DTU
P32 Martin Bundgaard Aarhus University
P33 Martin Frandsen Aarhus University
P34 Martin Juhl KU - KEMI
P35 Maryam Pirouz DTU
P36 Michael Bæk KU - FARMA
P37 Michael Martin Nielsen KU - KEMI
P38 Mujtaba Hassan Lund University
POSTER PRESENTATIONS LIST
P39 Nanna L. Nielsen Aarhus University
P40 Nicolaj Inunnguaq Jessen Aarhus University
P41 Niels Bisballe KU - KEMI
P42 Nina Gravesen Salinas KU - KEMI
P43 Oliver Gedde Aarhus University
P44 Rikke Asbæk Hansen Aarhus University
P45 Samuel Pedersen Aarhus University
P46 Sana Ma KU - FARMA
P47 Shirin Ahmadi DTU
P48 Simon Steffen Pedersen Aarhus University
P49 Simone Samuelsen DTU
P50 Steffen Gasbjerg Aarhus University
P51 Tamal Roy KU - KEMI
P52 Thomas Holmstrøm KU - KEMI
P53 Tiago Bozzola Lund University
P54 Veronika Chadimová Lund University
P55 Wallacec Reis Aarhus University
P56 Yue Xu KU - FARMA
POSTER PRESENTATIONS LIST
Alexander - +45 51 88 19 91
Vita - +45 52 71 06 21
Dominik - +45 42 72 67 76
Atrium
Aud 4
Cantina
MAP OF THE CAMPUS AREA
TOKS COMMITTEE CONTACTS
Name Organisation Supervisor
Alexander David Davies KU - FARMA Kristian Strømgaard
Alexander Lund Nielsen KU - FARMA Christian A. Olsen
Allan Petersen KU - FARMA Jiwoong Lee
Allesio Cataldo KU - KEMI Michael Pittelkow
Amalie Juul Aarhus University Kurt Gothelf
Anders Märcher Aarhus University Kurt Gothelf
Anders Skov KU - KEMI Theis Sølling
Anders Tolstrup KU - KEMI Mogens Brøndsted
Andrea Knakkergaard Knub KU - KEMI Mogens Brøndsted
Andreas Erichsen KU - KEMI Michael Pittelkow
Angel E. Santorelli Aarhus University Kurt Gothelf
Anne U. Petersen KU - KEMI Mogens Brøndsted
Argyro Tsakoumagkou KU - FARMA -
Asger Koue KU - KEMI Christian M. Pedersen
Aske Skyum Donslund Aarhus University Troels Skrydstrup
Bengt H. Gless KU - FARMA Christian A. Olsen
Benjamin Lukas Regen-Pregizer KU - KEMI Jiwoong-Lee
Bodil Lousen KU - KEMI Michael Pittelkow
Carlos Moreno KU - FARMA Christian A. Olsen
Casper Egholm Jensen KU - KEMI Michael Pittelkow
Charlotte Nybro Bjerking DTU Sophie R. Beeren
Christian Bartling KU - FARMA Kristian Strømgaard
Christian Danø KU - KEMI Mogens Brøndsted
Christian Marcus Pedersen KU - KEMI Christian M. Pedersen
Christina Schøttler Nielsen KU - KEMI Mogens Brøndsted
Christoffer Heidtmann SDU Poul Nielsen
Cindy Ng Aarhus University Kurt Gothelf
Daniel Raydan KU - KEMI Christian M. Pedersen
Daniela Dankova KU - FARMA Kristian Strømgaard
Danny Jørgensen Aarhus University Karl Anker Jørgensen
Dianna Andersen KU - KEMI Mogens Brøndsted
Dominik Essig KU - FARMA Kristian Strømgaard
Dorleta Chichon KU - FARMA Anders Bach
Eduardo Felipe Alves Fernandes KU - FARMA Kristian Strømgaard
Elena del Giorgio KU - KEMI Thomas Just Sørensen
Emilie Sperling Andreasen KU - KEMI Mogens Brøndsted
Erik Dampe KU - FARMA Anders Bach
Esben Svenningsen Aarhus University Thomas B. Poulsen
Esmeralda Bukuroshi KU - KEMI Mogens Brøndsted
Fadhil S. Kamounah KU - KEMI Michael Pittelkow
LIST OF PARTICIPANTS
Faidra Voukia SDU Poul Nielsen
Flora Alexopoulou KU - FARMA Kristian Strømgaard
Floriane Baussiere Lund University Ulf Nilsson
Frederik Kuhlman Dietre KU - KEMI Michael Pittelkow
Frederik Rostrup KU - FARMA Bente Frølund
Giordano Proietti SDU Jasmin Mecinović
Giorgia Masciotta DTU Sophie R. Beeren
Giusepp Marseglia KU - FARMA Anders Bach
Gustav Wørmer AU Thomas B. Poulsen
Hamza Ali Iqbal KU - KEMI Michael Pittelkow
Heleen de Jong KU - FARMA Bente Frølund
Helene Andersen KU - KEMI Thomas Just Sørensen
Henriette Natorp Tobiesen Aarhus University Karl Anker Jørgensen
Hugo Collin Aarhus University Troels Skrydstrup
Ida de Vries KU-FARMA Lennart Bunch
Jaime Moyano Villameriel KU - KEMI Christian M. Pedersen
Jakob Blom Aarhus University Karl Anker Jørgensen
Jakob Pallesen KU - FARMA Anders Bach
Javier Balboa KU - FARMA Kristian Strømgaard
Jens Voss SDU Poul Nielsen
Jesper Dahl Jensen KU - KEMI Bo Wegge Laursen
Jesper Mikkelsen Aarhus University Troels Skrydstrup
Jesper Tversted Christensen SDU Steffen Bähring
Jie Zang KU - FARMA Anders Bach
Jiyan Niclas Mandrup Kandemir KU - FARMA Christian A. Olsen
Joakim Bøgelund Jakobsen Aarhus University Troels Skrydstrup
Johannes Nygaard Lamhauge Aarhus University Karl Anker Jørgensen
Jonas Odgaard Petersen KU - FARMA Bente Frølund/Christoffer Clemmensen
Jordi Hintzen SDU Jasmin Mecinovic
Josefine Mogensen KU - KEMI Mogens Brøndsted
Kasper Beck SDU Poul Nielsen
Kassem El-Chami Aarhus University Kurt Gothelf
Katrine Domino Aarhus University Troels Skrydstrup
Kim Tran KU - FARMA Anders Bach
Kobra Azizi DTU Robert Madsen
Kristian Bjerggaard Olesen KU - KEMI Michael Pittelkow
Kristian Mark Jacobsen Aarhus University Thomas B. Poulsen
Lasse Brokmose Poulsen KU - KEMI Michael Pittelkow
Lea Nielsen KU - KEMI Thomas Just Sørensen
Levon Gzogian SDU Stefan Vogel
Lieke van Gijzel KU-FARMA Trond Ulven
Line Langhorn KU - KEMI Michael Pittelkow
Line Mouritsen Broløs KU - KEMI Mogens Brøndsted
Linette Ruder SDU Poul Nielsen
Lotte de Vries KU - KEMI Michael Pittelkow
Mads Christian Larsen SDU Steffen Bähring
Mads Georg Rasmussen KU - KEMI Mogens Brøndsted
Mads Koch Skaanning Aarhus University Kurt Gothelf
Mads Nybo Sørensen SDU Changzhu Wu
Maja E. T. Langballe Aarhus University Kurt Gothelf
Manuela Berto Pucca DTU Andreas Laustsen
Maria Cecilia Helleskov Thomsen KU - KEMI Mogens Brøndsted
Marie Louise Ploug SDU Steffen Bähring
Marko Heine Nowack SDU Jan O. Jeppesen
Martin Abildgaard KU - KEMI Mogens Brøndsted
Martin Bundgaard Aarhus University Troels Skrydstrup
Martin Frandsen Aarhus University Kurt Gothelf
Martin Juhl KU - KEMI Jiwoong Lee
Martin Kilde KU - KEMI Michael Pittelkow
Martin Roatch KU - FARMA Christian A. Olsen
Martina Luchini KU - FARMA Anders Bach
Maryam Pirouz DTU Robert Madsen
Mathias Lander Skavenborg SDU Jan O. Jeppesen
Mathias Simonsen Christensen SDU Jan O. Jeppesen
Mathias Stendorf Neumann SDU Steffen Bähring
Michael Bæk KU - FARMA Christian A. Olsen
Michael Martin Nielsen KU - KEMI Christian M. Pedersen
Morten Rewers KU - KEMI Michael Pittelkow
Mujtaba Hassan Lund University Ulf Nilsson
Nanna L. Nielsen Aarhus University Kurt Gothelf
Natasha Videcrantz Faurschou KU - KEMI Christian M. Pedersen
Nichlas Karer KU - KEMI Kristian Strømgaard
Nickie Lubrin KU - KEMI Mogens Brøndsted
Nicolai Hansen KU - KEMI Michael Pittelkow
Nicolaj Inunnguaq Jessen Aarhus University Karl Anker Jørgensen
Niels Bisballe KU - KEMI Bo Wegge Laursen
Niels Østergaard Hammer Aarhus University Karl Anker Jørgensen
Niklas Svenningsen KU - KEMI Mogens Brøndsted
Nikolaj Agertoft Lundquist KU - KEMI Christian M. Pedersen
Nina Gravesen Salinas KU - KEMI Bo Wegge Laursen
Nomaan Rezayee Aarhus University Karl Anker Jørgensen
Oliver Gedde Aarhus University Troels Skrydstrup
Oscar Moreno KU-FARMA Lennart Bunch
Oskar Ø. Bahlke KU - FARMA Christian A. Olsen
Patrycja Mala KU - KEMI Christian M. Pedersen
Per Hjerrild Aarhus University Thomas B. Poulsen
Rasmus Kragh KU - KEMI Ji-woong Lee
Rikke Asbæk Hansen Aarhus University Kurt Gothelf
Robert Luc Pham SDU Poul Nielsen
Rodrigo Flores de Alba SDU Stefan Vogel
Roman Gritcenko Lund University Ola F. Wendt
Samuel Pedersen Aarhus University Troels Skrydstrup
Sana Ma KU - FARMA Kristian Strømgaard
Shadi Reda Wahid SDU Stefan Vogel
Shirin Ahmadi DTU Andreas Hougaard Laustsen
Sif Tylvad Linde Aarhus University Karl Anker Jørgensen
Simon Steffen Pedersen Aarhus University Simon S. Pedersen
Simona Kotesova KU - FARMA Christian A. Olsen
Simone Hilt Bartholin KU - KEMI Christian M. Pedersen
Simone Samuelsen DTU Robert Madsen
Sofie Markussen KU - KEMI Michael Pittelkow
Steffen Bundgaard Andersen SDU Changzhu Wu
Steffen Gasbjerg Aarhus University Kurt Gothelf
Steffen Mogensen KU - KEMI Jiwoong-Lee
Stephan Pedersen KU - KEMI Michael Pittelkow
Stephan Ta SDU Changzhu Wu
Stine Hygum Sørensen SDU Poul Nielsen
Sylvester Petersen KU - FARMA Christian A. Olsen
Søren Christensen KU - KEMI Mogens Brøndsted
Tamal Roy KU - KEMI Jiwoong Lee
Thomas Holmstrøm KU - KEMI Christian M. Pedersen
Thomas Jul Sticker Olsen KU - KEMI Christian M. Pedersen
Thomas Whitmarsh-Everiss DTU Luca Laraia
Tiago Bozzola Lund University Ulf Ellervik
Veronika Chadimová Lund University Ulf Nilsson
Viktor B. R. Pedersen KU - KEMI Mogens Brøndsted
Vita Sereikaité KU - FARMA Kristian Strømgaard
Wallacec Reis Aarhus University Troels Skrydstrup
Yang Yang KU - KEMI Jiwoong Lee
Yongsong Tian KU - FARMA Bente Frølund
Yue Xu KU - FARMA Bente Frølund
Yulong Miao KU - FARMA Robert Madsen
Prof. Jean-Louis Reymond University of Bern Invited Speaker
Prof. Karl-Heinz Altmann ETH Zurich Invited Speaker
Prof. Kristian Strømgaard KU - FARMA DRA Host
Dr. Laurence Mulard Pasteur Paris Invited Speaker
