Department of Medicinal Chemistry2015 Annual Report

Weaver-Densford Hall308 Harvard Street Southeast

Cancer & Cardiovascular Research Building2231 Sixth Street Southeast

Minneapolis, MN

717 Delaware Building717 Delaware Street Southeast

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ContentsLetter from the Department Head ........................................................................... ii

Mission Statement ................................................................................................... 1

University News ....................................................................................................... 1

Teaching & Service .................................................................................................. 2

Institute for Therapeutics Discovery & Development ............................................... 3

Journal of Medicinal Chemistry ............................................................................... 3

Faculty Recognition: Awards & Promotions ............................................................. 4

Faculty Recognition: In the News ............................................................................ 4

Research Activities .................................................................................................. 5

Seminars ................................................................................................................. 6

Student Recognition ................................................................................................ 7

MIKI Meeting 2015 .................................................................................................. 9

Faculty ..................................................................................................................... 10

Adjunct Faculty ........................................................................................................ 10

Administrative Staff .................................................................................................. 11

Research Staff ......................................................................................................... 11

Postdocs, Fellows, & Visiting Scholars .................................................................... 12

Graduate Students .................................................................................................. 12

Undergraduate Research Assistants & Summer Scholars ...................................... 13

Ways to Give ........................................................................................................... 14

Research Grants ..................................................................................................... 14

Publications ............................................................................................................. 16

Photo Captions ........................................................................................................ 23

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Greetings!The year 2015 included many accomplishments in the Department of Medicinal Chemistry. Philip Portoghese was awarded the 2015 Takeru Higuchi Research Prize from the American Pharmacists Association Academy of Pharmaceutical Research and Science, was recognized at the APhA Annual Meeting in San Diego, and was named one of the top 25 pharmacy professors by Medical Technology Schools. I was elected a Member-at-Large of the Section on Pharmaceutical Sciences by the American Association for the Advancement of Science. David Ferguson was named Professor of the Semester 2015 by the PharmD Twin Cities class of 2019. Elizabeth Ambrose tied with Michael Swanoski for the Professor of the Semester Award by the PharmD class of 2017 (Twin Cities and Duluth).Financial support is vital to the function and continued success of our institution. The Department of Medicinal Chemistry and the ITDD received more than $6.5 million in research support from external agencies in calendar year 2015.

This year, we had 52 students in our graduate program and our faculty advised several students from other departments and the Mayo Clinic. We welcomed ten new students to the graduate program this fall and five students graduated. Departing students Ran Dai and Li-Kai Liu from the Finzel lab, Elbek Kurvanov from the Ambrose lab, Yang Li from the Fecik lab, and Margaret Olson from the Harki lab have moved on to pursue the next step in their research careers. The department also employs 60 postdoctoral and research associates.This was another successful year for our students. Elbek Kurbanov from the Ambrose lab was invited to present his research at the Graduate School’s 2015 Doctoral Research Showcase. Elbek Kubanov from the Ambrose lab and Adam Zarth from the Hecht lab received Doctoral Dissertation Fellowships (DDF) from the Graduate School. Kimberly Maize from the Finzel lab and Joseph Buonomo from the Aldrich lab were Bighley Graduate Fellowship Award winners. Kimberly Maize was also one of 10 recipients nationally to receive the Eli Lilly/WCC Travel Award. The American Foundation for Pharmaceutical Education (AFPE) Board of Directors selected Sara Coulup from my lab to receive an AFPE Pre-Doctoral Award in Pharmaceutical Science. Stephanie Breunig, an undergraduate in the Harki lab, was awarded a stipend and travel funds from the Undergraduate Research Opportunities Program for her project. Wagner lab member Aniekan Okon won a best poster award at the “Translation Machinery and Health: Protein Synthesis and Beyond” Gordon Research Conference. Cliff Csizmar from the Wagner lab has been awarded the Dr. Warren J. Warwick and Henrietta Holm Warwick Fellowship for 2015–16. John Widen from the Harki lab received a travel grant from the Division of Medicinal Chemistry to attend the 2015 National American Chemical Society Meeting. Finally, student worker Laura Burnes received a SELP award at the annual Student Employee Recognition Event, which recognizes exceptional student employees.I hope you share our pride in the Department’s accomplishments of 2015 and wish you all the best for the coming year.

Gunda Georg, Department Head

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The mission of the Department of Medicinal Chemistry is to educate and train scientists of the highest caliber, to provide future pharmacy practitioners with the basis for understanding the relationships between molecular structure and drug action, and to achieve and perpetuate excellence in medicinal chemistry through chemical and biological research for the improvement of human health.

Department of Medicinal Chemistry Head Gunda Georg is serving on the new campus-wide Grand Challenges Research Strategies group. The group has been charged with gathering perspectives from across campus on interdisciplinary areas of research and scholarship where the University has, or is poised to have, exceptional strength and a competitive advantage. In consultation with faculty, staff, students, and relevant external experts, they will then suggest which of these areas might best align with the Grand Challenge criteria outlined by the Strategic Planning Workgroup.

After more than 20 years as Dean of the College of Pharmacy, Dean Marilyn Speedie announced her retirement. The announcement was made February 2015. Speedie will stay on as Dean while the recruiting process continues and will step down when a new leader is chosen.Dean Speedie commented on her decision, “While the decision to step down wasn’t easy, I believe the timing is right for a leadership transition. Within the next few months we will have launched the last year of our new curriculum, and we recently successfully completed accreditation requirements set forth by ACPE. The college overall is in a strong position for a change in leadership.”

Dr. Sunil David joined the Department of Medicinal Chemistry in August. Dr. David is known for his work in adjuvant vaccine development, infectious disease, immunology, and inflammatory disease processes. Researchers from his group at the University of Kansas joined him in his new lab in the Cancer & Cardiovascular Research Building.

Mission Statement University News

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Teaching & ServiceMedicinal Chemistry faculty members taught numerous professional and graduate courses in 2015 and were recognized throughout the year for high-quality teaching and dedication to students.Faculty also contributed to numerous committees, representing service to the Department, the University, the College of Pharmacy, national and professional organizations, and government agencies.Professor Barry Finzel has been nominated to serve a three-year term as a USenate representative for the College of Pharmacy; he joins Elizabeth Ambrose who is also serving through 2016.Additionally, numerous faculty served as reviewers for professional journals and as grant reviewers for governmental panels.

Graduate Courses• Introduction to Drug Design (MEDC 5245) • Principles of Medicinal Chemistry I (MEDC 8001)• Principles of Medicinal Chemistry II (MEDC 8002)• Recitation in Mechanistic Organic Chemistry

(MEDC 8050)• Medicinal Chemistry Seminar (MEDC 8100)• Design of Chemotherapeutic Agents (MEDC 8500)• Bioassay & Data Analysis (MEDC 8435)• Molecular Targets of Drug Design (MEDC 8753)• Medicinal Chemistry Laboratory Techniques

(MEDC 8800)• Research in Medicinal Chemistry (MEDC 8900)

Professional Courses• Drugs of Abuse (PHAR 4248 and 6248)• Honors Course: Medicinal Chemistry Seminar

(PHAR 6150)• Introduction to Pharmacy Research (PHAR 6206)• Integrated Biochemical Sciences (PHAR 6702)• Pharmaceutical Care Skills Lab I (PHAR 6710)• Applied Pharmaceutical Care (PHAR 6716)• Pharmaceutical Care Skills Lab II (PHAR 6720)• Principles of Medicinal Chemistry (PHAR 6722)• Immune System & Infectious Disease (PHAR 6724)• Principles of Pharmacology (PHAR 6726)• Medicinal Chemistry & Pharmacology of

Cardiovascular Drugs (PHAR 6732)• Cellular Metabolism & Nutrition (PHAR 6734)• Colloquium I: Scholarly Presentation Skills

(PHAR 6742)• Integrated Endocrinology (PHAR 6752)• Diabetes & Metabolic Syndrome (PHAR 6754)• Medicinal Chemistry and Neuropharmacology

(PHAR 6762)• Biotechnology Derived Drugs (PHAR 6768)• Infectious Disease (PHAR 6768)• Oncology (PHAR 6784)

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Institute for Therapeutics Discovery & DevelopmentThe Institute for Therapeutics Discovery and Development (ITDD) continued its research projects in the areas of drug discovery and development, and provided services to the scientific community of the University of Minnesota, the State of Minnesota, and beyond. The Institute has continued its effort toward developing non-hormonal male and female contraception. The highly innovative and collaborative program led by Dr. Gunda I. Georg, the Institute Director, has had continuous multi-million dollar funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for over a decade. The ITDD neuroscience program, with a primary focus on finding a cure for Alzheimer’s disease, is led by Dr. Michael A. Walters, Director of the Lead and Probe Discovery Core. Dr. Peter I. Dosa has continued his efforts in moving the anti-glaucoma lead candidate into preclinical development. The program is a collaboration with the Mayo Clinic and is currently supported by the Minnesota Partnership for Biotechnology and Medical Genomics with a multi-year grant. Dr. Walters, in collaboration with the Mayo Clinic and support from the same program, began a similar two-year project in 2015 to develop agents to treat aortic valve calcification. Dr. Jon Hawkinson, Director of the High-Throughput Screening and Assay Development Core, was awarded a shared instrumentation grant by the National Institutes of Health (NIH) to purchase a cutting-edge Biacore S200 surface plasmon resonance (SPR) instrument. The new equipment will significantly enhance the screening capability of the ITDD.

The Therapeutics Process Development Core led by Dr. Vadim J. Gurvich, the ITDD’s Associate Director, has participated in several drug development programs funded by the NIH, U.S. Department of the Army, private industry, and internal University sources. The programs are focused on various therapeutic areas such as asthma, atrial fibrillation, prostate cancer, bladder cancer, and others. Most recently, Dr. Gurvich was awarded a SBIR grant in collaboration with Blue Therapeutics, a Boston-based start-up pursuing commercialization of novel non-addictive analgesic agents originally developed in the Department of Medicinal Chemistry. Additionally, the ITDD has forged collaborations with several pharmaceutical companies, including two locally (effort led by Drs. Jon Hawkinson and Henry Wong), providing its services and expertise in various areas of drug discovery and development.

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Gunda Georg has been elected a Member-at-Large of the Section on Pharmaceutical Sciences by the American Association for the Advancement of Science. Her four-year term began February 2015. The American Pharmacists Association Academy of Pharmaceutical Research and Science honored Distinguished Professor Philip Portoghese with the 2015 Takeru Higuchi Research Prize. This award recognizes the highest accomplishments in pharmaceutical sciences, and is international in scope and stature. Dr. Portoghese was recognized at the APhA Annual Meeting in San Diego in March. He was also named one of the top 25 pharmacy professors by Medical Technology Schools.David Ferguson was named Professor of the Semester 2015 by the PharmD Twin Cities class of 2019. Elizabeth Ambrose tied with Michael Swanoski for the Professor of the Semester Award by the PharmD class of 2017 (Twin Cities and Duluth).

Faculty Recognition: Awards & Promotions

Faculty Recognition: In the NewsThe Grand Forks Herald article “Grand Forks Police Investigating ‘Drug New to North Dakota’” included quotes from David Ferguson about the illegal use of powdered fentanyl.In the Health Talk feature “Promising Research for a New Antibiotic” Courtney Aldrich explains the importance of a new antibiotic study recently published in Nature.

The American Chemical Society (ACS) Journal of Medicinal Chemistry is the most-cited journal in medicinal chemistry and ranked as the top primary research journal in impact in its category. Gunda Georg is co-Editor-in-Chief with Shaomeng Wang at the University of Michigan Comprehensive Cancer Center. Carrie Haskell-Luevano also serves as Executive Editor.

Journal of Medicinal Chemistry

The University of Minnesota now boasts five Editors-in-Chief of ACS journals, the most in the country. Courtney Aldrich is the Editor-in-Chief of the new ACS journal, Infectious Diseases, which began accepting papers in the fall for the first issue in January 2015. Rick Wagner is the Executive Editor of Molecular Pharmaceutics, and Stephen Hecht serves as Editor-in-Chief of Chemical Research in Toxicology.

Medicinal Chemistry Faculty Editors

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Research ActivitiesDepartment of Medicinal Chemistry graduate faculty produced 91 publications in more than 54 journals and presented at numerous conferences through oral and poster presentations in 2015.

The University of Minnesota has been selected by the National Institutes of Health as one of three Research Evaluation and Commercialization Hub (REACH) sites nationally to establish a university-wide strategic framework promoting commercialization and technology transfer in the life sciences and biomedical technology. Supported by a $3 million NIH grant with another $3 million in matching U of M funds, the university’s MN-REACH program will provide commercial expertise and resources needed for the development and commercialization of diagnostics, therapeutics, preventive medicine, and medical devices. The program will establish new industry partnerships, strengthen existing partnerships, and provide entrepreneurial, commercial-style education for innovators to accelerate the pace at which innovations reach the marketplace.

The team for this project includes ITDD Director Vadim Gurvich, who will co-lead the pharmaceutical side of the program. Charles Muscoplat, College of Food, Agricultural and Natural Resources Science, will lead MN-REACH, while Allison Hubel, BioCoR Director will direct the medical device aspects. Additonally, Kevin Peterson from the Department of Community Health and the Center for Excellence in Primary Care will provide medical advice and oversight.

The U.S. News & World Report feature “The Future of Male Birth Control” includes a profile of Gamendazole, the male birth control pill being developed by Gunda Georg with Joseph Tash from the University of Kansas.

Stephen Hecht was quoted in the story “Wisconsin Lawmakers Work to Catch Up with the E-cigarette Boom” on Wisconsin Public Radio and in the Superior Telegram.

Michael A. Walters, his Mayo Ph.D. student Jayme Dahlin, and their collaborators including Jessica Strasser and Subhashree Francis (both from the Walters lab) had a featured article in the Journal of Medicinal Chemistry, “PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed During a Sulfhydryl-Scavenging HTS.”

“Chemistry: Chemical Con Artists Foil Drug Discovery,” a commentary co-authored by Michael Walters, ITDD Lead and Probe Discovery Core Director, was published in Nature on September 24th. The article warns that research naivety about promiscuous, assay-duping molecules is polluting the literature and wasting resources.

Faculty Recognition: In the News (Continued)

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Other seminars in 2015 by the Department of Medicinal Chemistry, the Chemical Biology Initiative (CBI), and the Institute for Therapeutics Discovery & Development (ITDD) are listed below.

• Dr. Donald Lo, Duke University, “3-D Brain Tissue Models for CNS Drug Discovery: Adventures with Natural & Unnatural Products,” January 27.

• Dr. Erin Carlson, University of Minnesota, “Chemical Probes for Histidine Kinase Profiling & Inhibitor Discovery,” February 10.

• Dr. Peter Madrid, the Center for Chemical Biology, SRI, “Anti-infective Drug Discovery at a Non-Profit Institute: 1) New Drugs for TB & 2) Drug Re-purposing for Ebola,” February 24.

• Dr. Allen Reitz, Institute for Hepatitis and Virus Research (IHVR), Pennsylvania Drug Discovery Institute at the University of Pennsylvania, “Chemical & Structural Biology of Epstein-Barr Nuclear Antigen EBNA12 & Derivatives of Myricanol that Autophagic Tau Clearance,” March 3.

Seminars

Dr. Bryan Roth, University of North Carolina at Chapel Hill, presented the second Portoghese lecture, “Genome Wide Approaches to GPCR Chemical Biology.” Dr. Craig Lindsley, Vanderbilt University, gave the third Portoghese lecture, “Allosteric Modulation Targeting mGlu1 and PLD: New Insights and Therapeutic Potential.”

There were four Distinguished Lectureships given this year. Dr. Frank Raushel from Texas A&M University presented “Evolution of Enzymes for Catalytic Hydrolysis of Organophosphate Nerve Agents.” Dr. Kim Janda from The Scripps Research Institute gave the distinguished lecture “Merging of Chemistry and Biology: In Search of Molecules with Translational Function.” Dr. Joel Barrish, Vice President of Discovery Chemistry at Bristol-Myers Squibb, presented “Innovation in Kinase Inhibitor Drug Discovery: Evolution of a Drug Target Class.” Finally, Dr. Barbara Timmermann from the University of Kansas gave the distinguished lecture “ Discovery and Investigation of Therapeutically Important Plant Natural Products.”

Hecht lab member Adam Zarth presented the Abul-Hajj-Hanna Exceptional Graduate Student Seminar, “Analyses of the Metabolism and Detoxification or DNA Damage of the Human Carcinogens Benzene and N’-Nitrosonornicotine.”

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• Dr. William Chain, University of Hawaii at Manoa, “Chemistry and Biology of Englerin A,” April 14.

• Dr. David Chenoweth, University of Pennsylvania, “Chemical Approaches to Probing, Manipulating, and Imaging Biological Systems,” May 5.

• Dr. James Wollack, St. Catherine University, “Site-specific Enzymatic Modification of CAAX Containing Proteins with Bioorthogonal Tags Capable of Strain Promoted Cyclcoaddition,” June 23.

• Dr. Nadja Cech, University of North Carolina at Greensboro, “Mass Spectrometry Based Metabolomics to Identify Active Compounds In Natural Product Mixtures,” September 29.

• Dr. Daniel Erlanson, President of Carmot Therapeutics, “Fishing for Drug Fragments and Leads,” October 13.

• Dr. Jonathan Vennerstrom, University of Nebraska Medical Center, “Discovery of Antimalarial Ozonides OZ277 and OZ439,” December 8.

• Dr. Jerod Skyberg, College of Veterinary Medicine, University of Missouri, “Medicinal Chemistry Immunity of Brucellosis and Tularemia,” December 15.

Seminars (continued)

Student RecognitionFifty-two students enrolled in the graduate program this year. Five students graduated, and ten students joined the department: Malcolm Cole, Amanda Degner, Anand Divakaran, Corey Geehan, Ellie Hofer, Dmitri Konorev, William McCue, Connor McDermott, Kathryn Schlasner, and John Schultz.

As usual, our students were recognized and rewarded for the caliber of their work.

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Student Recognition (continued)

Elbek Kurbanov of the Ambrose lab was invited to present his research on Computational, Synthetic, Biochemical, and X-ray Crystallographic Methods for Anthrax Toxin Lethal Factor (LF) Inhibitor Design at the Graduate School’s 2015 Doctoral Research Showcase. Elbek Kurbanov also received a 2014–15 Doctoral Dissertation Fellowship (DDF) from the Graduate School for this research. Adam Zarth of the Hecht lab was awarded a 2015–16 Doctoral Dissertation Fellowship from the Graduate School. The DDF allows the University’s most accomplished Ph.D. candidates to devote full-time eff ort to an outstanding research project by providing time to fi nalize and write a dissertation during the fellowship year. Adam was also the second recipient of the Department’s Abul-Hajj–Hanna Exceptional Graduate Student Award in Medicinal Chemistry. The award honors individual excellence among graduate students based on quantity and quality of research accomplishments, original research proposal for the oral exam, quality of seminars, grade-point average since entering

the program, and service and citizenship in departmental aff airs. The award includes a cash prize. Kimberly Maize of the Finzel lab and Joseph Buonomo of the Aldrich lab were two of four Bighley Graduate Fellowship Award Winners for 2015–16. Kimberly Maize was one of 10 recipients nationally of the Eli Lilly/WCC Travel Award.The American Foundation for Pharmaceutical Education (AFPE) Board of Directors selected Sara Coulup, a graduate student in the Georg lab, to receive a $10,000 AFPE Pre-Doctoral Award in Pharmaceutical Science.Stephanie Breunig, an undergraduate chemistry major of the Harki lab has received an Undergraduate Research Opportunities Program (UROP) award for her project “The Synthesis of APOBEC3G Reversible Covalent Inhibitors.” She will continue working in the Harki lab this summer with her second Department of Chemistry Heisig/Gleysteen summer research fellowship. The fellowship includes a summer stipend and travel to a scientifi c conference to present research results.

Wagner lab member Aniekan Okon won a best poster award at the “Translation Machinery and Health: Protein Synthesis and Beyond” Gordon Research Conference.Cliff Csizmar, a member of the Wagner lab, has been awarded the Dr. Warren J. Warwick and Henriett a Holm Warwick Fellowship for 2015–16. This fellowship includes a stipend and research grant totaling $30,000.Graduate student John Widen, a member of the Harki lab, received a $1,000 travel grant from the Division of Medicinal Chemistry (MEDI) to att end the 2015 National American Chemical Society Meeting in Boston in August where he presented a poster of his research.Student worker Laura Burnes received a SELPie award on May 7th at the annual Student Employee Recognition Event. The Student Employee Leadership Program (SELP) recognizes student employees who go above and beyond expectations in their work at the university.

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More than 100 graduate students, postdocs, and faculty members from more than ten departments attended the annual National Institutes of Health Chemistry-Biology Interface Training Grant (CBITG) Symposium in May. The symposium was planned and hosted by current CBITG trainees, including Department of Medicinal Chemistry students Sara Coulup (Georg lab) and Carter Eiden (Aldrich lab). A variety of speakers from fields that bridge chemistry and biology research presented a range of topics. Kim Maize (Finzel lab) presented “Ligand-Induced Structural Changes in Anthrax Lethal Factor.” In addition, the symposium featured a poster session where the department was well-represented by graduate students Joe Buonomo and Carter Eiden (Aldrich lab); Denise Casemore (Xing lab); Sara Coulup, David Huang, and Andrea Wisniewski (Georg lab); Arnie Groehler (Tretyakova lab); Elbek Kurvanov (Ambrose lab); Cody Lensing (Haskell-Luevano lab); Aniekan Okon (Wagner lab); and Margaret Olson and John Widen (Harki lab).

CBITG Symposium 2015

Student Recognition (Continued)

Held annually since 1963, the MIKI “meeting-in-miniature” is the oldest and most successful regional meeting in medicinal chemistry. Rotating meetings are organized by medicinal chemistry graduate students at the Universities of Minnesota, Iowa, Kansas, and Illinois at Chicago. The University of Kansas hosted the 53rd Annual MIKI meeting, which featured a keynote lecture by Bruce Roth, the Senior Vice President of Small Molecule Drug Discovery at Genentech. Graduate students Elbek Kurbanov (Ambrose lab), Jingjing Shen (Wagner lab), Adam Zarth (Hecht lab), and Bo Zhou (Xing lab) made presentations on behalf of the University of Minnesota.

MIKI Meeting 2015

CommencementRan Dai ........................................................Ph.D., January ...............................................................Advisor: Finzel “Fragment Based Inhibitor Design of Mycobacterium tuberculosis BioA”Elbek Kurbanov .........................................Ph.D., October ..............................................................Advisor: Ambrose “Synthetic, Biochemical, X-ray Crystallographic, Computational and High-Throughput Screening Approaches Toward Anthrax Toxin Lethal Factor Inhibition”Yang Li ..........................................................Ph.D., July .....................................................................Advisor: Fecik “Deciphering Cryptic Stereochemistry in Polyketide Biosynthesis and Functional Characterization of B-processing Domains in Pikromycin Synthase”Li-Kai Liu .....................................................Ph.D., August ................................................................ Advisor: Finzel “Discovery of Small Molecular Inhibitors of Hyaluronan Binding at Cell Receptor CD44”Margaret Olson ...........................................Ph.D., September ......................................................... Advisor: Harki “High-Throughput Screening and Chemical Synthesis for the Discovery of APOBEC3 DNA Cytosine Deaminase Inhibitors”

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FacultyGunda I. Georg ......................Department Head and Professor; Director, Institute for Therapeutics Discovery & Development (ITDD); Robert Vince Endowed Chair and McKnight ChairRodney L. Johnson ................Associate Department Head and Distinguished ProfessorDavid M. Ferguson ...............Director of Graduate Studies and ProfessorYusuf J. Abul-Hajj .................ProfessorEyup Akgün ...........................Research Associate ProfessorCourtney C. Aldrich .............Associate Professor Elizabeth A. Ambrose ...........Associate ProfessorRebecca A. Cuellar ................Research Assistant ProfessorPeter I. Dosa ...........................Research Assistant Professor; Director, ITDD Medicinal Chemistry CoreEarl W. Dunham ....................Associate ProfessorRobert A. Fecik ......................Associate ProfessorBarry C. Finzel .......................ProfessorVadim J. Gurvich ...................Research Associate Professor; Associate Director, ITDD; Director, ITDD Chemical Process Development CorePatrick E. Hanna ....................Professor EmeritusDaniel A. Harki ......................Assistant ProfessorCarrie Haskell-Luevano .......Professor; Philip S. Portoghese Endowed Chair in Chemical Neuroscience; Institute for Translational Neuroscience ScholarJon Hawkinson ......................Research Professor; Director, ITDD High-Throughput Screening and Assay Development CoreSidath C. Kumarapperuma ..Research Assistant ProfessorHerbert T. Nagasawa ............Professor EmeritusPhilip S. Portoghese ..............Distinguished ProfessorRory P. Remmel .....................Distinguished Teaching ProfessorW. Thomas Shier ...................Professor Marilyn K. Speedie................Dean, College of Pharmacy; ProfessorNatalia Y. Tretyakova ...........ProfessorRobert Turesky ......................ProfessorCarston R. (Rick) Wagner .....Professor; Endowed Chair in Medicinal ChemistryMichael A. Walters ................Research Associate Professor; Director, ITDD Lead and Probe Discovery CoreHenry L. Wong ......................Research Associate Professor; Director, ITDD Pharmacology and Biomarkers CoreChengguo (Chris) Xing ........Professor

Adjunct Graduate FacultyMark D. Distefano .................Distinguished McKnight Professor, Department of ChemistryStephen S. Hecht ...................Professor, Wallin Chair Cancer Prevention, Masonic Cancer CenterThomas R. Hoye ....................Distinguished Teaching Professor, Department of ChemistryLisa A. Peterson .....................Professor, Division of Environmental Health SciencesValérie C. Pierre .....................Associate Professor, Department of ChemistryWilliam C. Pomerantz. ..........Assistant Professor, Department of Chemistry

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Administrative Staff

Research Staff

Caitlin Boley ...........................Executive Operations Student Services Specialist Laura Burnes ..........................Student Office AssistantMary Crosson ........................Associate AdministratorCaitlyn Dibble ........................Executive Office and Administrative Specialist Sandy Dewing .........................Associate Administrator, Journal of Medicinal ChemistryJeanine Ferguson ...................Assistant to Dr. Gunda GeorgHatdexa Nanatharn ..............Principal Office and Administrative SpecialistApoorva Reddy .....................Student Office AssistantRachel Rud .............................Executive Accounts SpecialistLeah Peck ................................Executive Office and Administrative SpecialistSarah Johnson Sexton ...........Executive Office and Administrative SpecialistAmy Xiong .............................Student Office Assistant

Danielle Adank ...................... Junior Scientist, Haskell-Luevano LabNarsihmulu Cheryala ...........Principal Scientist, Georg LabTing-Lan Chiu........................Research Associate, Ambrose Lab Matthew Cuellar ....................Principal Scientist, Walters LabRawle Francis .........................Principal Scientist, Hawkinson LabKatie Freeman ........................Assistant Scientist, Haskell-Luevano LabJoe Hexum .............................. Junior Scientist, Harki LabKwon Ho Hong .....................Research Associate, Georg Lab Sudhakar Jakkaraj .................Senior Principal Scientist, Georg LabKristen John ...........................Assistant Scientist, Hawkinson LabSesha Krishnamachari ..........Senior Scientist, Turesky Lab Peter Larson ...........................Senior Lab Technician, Ferguson LabMorgan Le Naour ..................Research Associate, Walters LabShuang Liang .........................Scientist, Gurvich Lab Pablo Leitzman ......................Senior Lab Technician, Xing LabLev Lis .....................................Principal Scientist, Gurvich LabMary Lunzer ..........................Scientist, Portoghese Lab Angela Perkins .......................Research Associate, Harki LabMichael Powers .....................Scientist, Portoghese Lab Sathya Schnell ........................ Junior Scientist, Haskell-Luevano Lab Stephen Schnell .....................Scientist, Portoghese LabAnamika Singh ......................Research Associate, Haskell-Luevano LabRondedrick Sinville ...............Principal Scientist, Hawkinson LabJonathan Solberg ...................Assistant Scientist, Hawkinson LabJessica Strasser .......................Assistant Scientist, Walters LabShameem Sultana Syeda ......Principal Scientist, Georg LabSrinivasa Tala .........................Research Associate, Haskell-Luevano LabDefeng Tian ............................Principal Scientist, Hawkinson Lab

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Kathryn Trautman ................Research Professional, David Lab Timothy Ward ........................Principal Scientist, Georg LabStacey Wilber .........................Scientist, Haskell-Luevano LabLihua Yao ................................Assistant Scientist, Turesky LabByeong Hwa (BH) Yun .........Research Associate, Turesky Lab

Mohamed Abou-Karam .......Shier LabTengfei Bian ............................Xing LabJin Cai ......................................Visiting Professor, Georg LabTingting Cai ...........................Turesky LabJanardhan Banothu ...............David LabMallesh Beesu ........................David LabDibyendu Dana .....................Harki LabSurendra Dawadi ..................Aldrich LabBassem Elsnerbini .................Visiting University Fellow, Shier LabMark Ericson ..........................Haskell-Luevano LabKate Guo .................................Turesky LabLeila Hejazi.............................Turesky LabYaisr Ihtesham .......................Shier Lab

Lakmal Kotelawala ...............Wanger LabFeng Liu ..................................Aldrich LabYupeng Li ...............................David LabZhenyuan Miao .....................Georg LabSreekanth Narayanapillai ....Xing LabKathryn Nelson .....................Walters LabFatemah Oroojalian ...............Shier LabKhyatiben (Kathy) Pathak ....Turesky LabJean Santos .............................Georg LabKristen Stoltz ..........................Dosa LabZinayyera Subhani ................Shier LabYi Wang ...................................Turesky LabYoshi Watanabe .....................Portoghese LabXi Zong ...................................Visiting Graduate Student, Georg Lab

Research Staff (Continued)

Postdocs, Fellows, & Visiting Scholars

Evan Alexander .................. Advisor: AldrichMatthew Bockman ............. Advisor: AldrichEmily Boldry ....................... Advisor: TretyakovaJoseph Buonomo ................ Advisor: AldrichErick Carlson ....................... Advisor: GeorgDenise Casemore ................ Advisor: XingMalcolm Cole ...................... Advisor: AldrichSarah Coulup ...................... Advisor: GeorgClifford Csizmar ................. Advisor: Wagner

Graduate StudentsAnand Divakaran ............... Advisor: PomerantzAmanda Degner ................. Advisor: TretyakovaSkye Doering ....................... Advisor: Haskell-LuevanoCarter Eiden ........................ Advisor: AldrichJenna Fernandez ................. Advisor: TretyakovaWilliam Fiers ....................... Advisor: FecikKatlyn Fleming ................... Advisor: Haskell-LuevanoCorey Geehan ..................... Advisor: XingArnold Groehler IV ............ Advisor: Tretyakova

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Molly Andersen .....................Tretyakova LabJordan Baur ............................Harki LabAlexandra Behrend ...............Tretyakova LabHarrison Berg ........................Ferguson LabStephanie Breunig .................Harki LabChris Brown ...........................Aldrich LabTenley Brown .........................Harki LabMaram Essaway ....................Aldrich LabMitch Fuller ............................Aldrich LabErick Gaasedelen ...................Aldrich LabRyan Harding ........................Remmel LabAlex Hendricks ......................Wagner labRyan Herzig ...........................Georg Lab

Undergraduate Research Assistants & Summer ScholarsEdward Higgins ....................Shier LabAbby Hoffman .......................Tretyakova LabMitch Hooverman .................Remmel LabBo Hu (Pharm.D.) ..................Harki LabTim Isdahl ..............................Wagner LabEmma King ............................Aldrich LabMolly Koller ...........................Haskell-Luevano LabDa Yeon Lee ...........................Xing LabJordan Paladinog ...................Xing LabJoshua Schmidt ......................Tretyakova LabMei Kuen Tang ......................Finzel LabEnoch You ...............................Aldrich LabAndrew Zhou ........................Wagner Lab

Graduate Students (Continued)Xianghong Guan ...................Advisor: GeorgEllie Hofer ..............................Advisor: WagnerTrinh (Amy) Holth ................Advisor: Georg David Huang .........................Advisor: GeorgShaofei Ji (Chem) ...................Advisor: TretyakovaJiewei Jiang .............................Advisor: GeorgOzgun Kilic ............................Advisor: WagnerDmitri Konorev .....................Advisor: TureskyElbek Kurbanov .....................Advisor: AmbroseJillian Kyzer ............................Advisor: GeorgCody Lensing ..........................Advisor: Haskell-LuevanoWei Li (Chem) ........................Advisor: GeorgYang Li ....................................Advisor: FecikJing Liu (Chem) .....................Advisor: WagnerKimberly Maize .....................Advisor: FinzelWilliam McCue ......................Advisor: FinzelConnor McDermott ...............Advisor: AmbroseAniekan Okon ........................Advisor: Wagner

Margaret Olson ......................Advisor: HarkiKellan Passow ........................Advisor: HarkiJacob Petersburg ....................Advisor: WagnerChris Richards (Pharmacol)..Advisor: HarkiKatherine Schlasner................Advisor: Haskell-LuevanoJohn Schultz............................Advisor: AldrichChristopher Seiler .................Advisor: TretyakovaRachit Shah.............................Advisor: WagnerJingjing Shen ..........................Advisor: WagnerAlex Strom ..............................Advisor: WagnerNicholas Struntz ....................Advisor: Harki Harrison (Trent) West ...........Advisor: WagnerJohn Widen .............................Advisor: HarkiAndrea Wisniewski ...............Advisor: GeorgAdam Zarth ............................Advisor: HechtBo Zhou ..................................Advisor: Xing

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Private support of our activities is important to maintain the quality of our program and the continuation of the mission of the department. Even small contributions accumulate over time and can have a significant impact.

Opportunities for giving include:• Abul-Hajj–Hanna Exceptional Graduate Student Award in Medicinal Chemistry• Medicinal Chemistry Alumni Graduate Student Fellowship• MIKI Meeting Fund• Ole Gisvold Fellowship in Medicinal Chemistry• Philip S. Portoghese Fellowship in Medicinal Chemistry• Philip S. Portoghese Lectures in Medicinal Chemistry• Remmel and Zimmerman Fellowship in Drug Metabolism and Pharmacokinetics• Robert Vince Graduate Student Fellowships• Taito O. Soine Lectures in Medicinal Chemistry• Yusuf J. Abul-Hajj Fellowship in Medicinal Chemistry

Our Development Director Robert Busch will work with you and answer any questions that you might have. He can be reached by e-mail, busch110@umn.edu, or phone (1-866-437-0012).

Ways to Give

Research GrantsOther ongoing projects and grants newly funded in 2015 are listed below with their primary investigator.

• Administration of the National Institute for Pharmaceutical Technology and Education ...........................................................................................................................Vadim Gurvich

• Anthrax Toxin Lethal Factor Inhibition Study ..............................................................Elizabeth Ambrose• Anti-cancer CSANs Development ...................................................................................Carston Wagner• Antitubercular Bir A Inhibitors ........................................................................................Courtney Aldrich• APOBEC3 Inhibitors ..........................................................................................................Daniel Harki/Margaret Olson• Beyond Parthenolide: Next Generation Molecules Targeting AML Cancer

Stem Cells ................................................................................................................................. Daniel Harki• Cell-cycle Regulatory Kinases as Targets for Male Contraceptive Drug

Development....... ..................................................................................................................... Gunda Georg• Cellular Effects of Small Molecule Antagonists of Hyaluronan Binding to CD44 ...Barry Finzel• Chemical Biology Consortium .........................................................................................Gunda Georg • Chemical Probes of Endogenous Mutation: Small Molecule Computational

and Experimental Optimization of Anthrax Toxin Lethal Factor (LF) Inhibitors ...Elizabeth Ambrose• Chemoproteomics Profiling of Parthenolinde in Human Glioblastoma ...................Daniel Harki• Critical Interactions of APOBEC3s ..................................................................................Daniel Harki• Critical Path Manufacturing Sector Research Initiative ...............................................Vadim Gurvich• Defensins as Melanocortin Ligands ................................................................................Carrie Haskell-Luevano• Design of Antibacterial Agents that Target Biotin Met ................................................Courtney Aldrich • Design of Antituberculosis Agents ..................................................................................Barry Finzel• Design of Antituberculosis Agents that Target Sidephore B .......................................Courtney Aldrich• Developing a Post-carcinogen Lung Cancer Chemopreventive .................................Chris Xing• Development of Photochemical DNA Decoys to Control NFkB Gene Expression .... Daniel Harki/Nicholas Struntz• Development of Pironetin as an Ovarian Cancer Chemo-therapeutic Agent ...........Gunda Georg/David Huang• Dihydromethysticin (DHM) for Lung Cancer Chemoprevention ..............................Chris Xing• Discovery of Small Molecule Inhibitors of Hyaluronan Binding ...............................Barry Finzel/Li-Kai Liu• DNA-Protein Cross-links: Cellular Effects and Repair Mechanisms .........................Natalia Tretyakova• DNA Cross-linking by Diepoxybutane........................................................................... Natalia Tretyakova

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• Drug Discovery and Synthesis of Contraceptive Agents .............................................Gunda Georg • Effect of MCC22, a New Mu Opioid Agonist & Hyperalgesia in Mice .....................Philip Portoghese• Engineering Cell–Cell Interactions by Chemically Self-assembled CARS ................Carston Wagner• Establishment, Colonization, Toxin Production and Development of Charcoal

Rot Fungus Macrophomina Phaseolina on Soybean During the Disease Life Cycle: Basic Biology ...........................................................................................................W. Thomas Shier

• FadD32: High-Throughput Screening & Inhibitor Synthesis .....................................Courtney Aldrich• Formulation Development and Manufacturing of Propofol Hemisuccinate ............Vadim Gurvich• Human Histidine Triad Nucleotide Binding Proteins (hHINT) .................................Barry Finzel/Kim Maize• Inhibitors of Na,K-ATPase Alpha4 as Male Contraceptives ........................................Gunda Georg• iTC200 MicroCalorimetry Cell Control Unit .................................................................Courtney Aldrich• Ligands that Target Opioid-chemokine and Opioid-mGlu5 Heteromers .................Philip Portoghese• Maintenance and Operation of a Medicinal Chemistry Facility .................................Gunda Georg• Mechanisms of Anticancer Agents Selective against Drug Resistant Leukemia ......Chris Xing • Mechanisms of Ethnic/Racial Differences in Lung Cancer ..........................................Natalia Tretyakova• Mechanisms of Prostate Cancer Prevention by Korean Angelica ...............................Chris Xing• Melanocortin Selective Ligands .......................................................................................Carrie Haskell-Luevano• Molecular Profiling of EPI-001: An Inhibitor of Androgen Receptor Signaling

with a Disputed Mechanism of Action ...........................................................................Daniel Harki • Novel Therapeutic Agents for the Treatment of Glaucoma ........................................Peter Dosa• Preclinical Development of Myosolvins, a New Class of Medicine for Asthma ......Vadim Gurvich• Production of Human MUC17 (CRD1-L-CRD2) Recombinant Protein in Rice ....... Jon Hawkinson• Role of DNA Deamination in Breast Cancer. ................................................................Daniel Harki• SERCA Activators for a Breakthrough in Diabetes Therapy ......................................Courtney Aldrich• Targeting Childhood Brain Tumors with Parthenolide Analogues ...........................Daniel Harki• Toward a Mechanism-based Approach to Treating Atrial Fib ....................................Vadim Gurvich • Design of Ligands to Inhibit Progression of Neurodegenerative Diseases. ..............Philip Portoghese • Enzyme-catalyzed Mutation in Breast Cancer .............................................................Daniel Harki• Excretion of Antibiotic Metabolite in the Broiler Chick following Hatchery

Antibiotic Administration ...............................................................................................Rory Remmel• Highly Potent Chemopreventive Agent Blocking Tobacco Carcinogen

4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced Lung Tumorigenesis & Mechanisms .........................................................................................Chris Xing

• Nano-engineered Mesenchymal Stem Cells as Targeted Therapeutic Carriers .......Natalia Tretyakova• Nuclear Export of Androgen Receptor with Light-controllable DNA Decoys .........Daniel Harki• Technology Platform for Development of Multi-component Preservation Solutions ...Peter Dosa• Treatment of Tauopathies .................................................................................................Michael Walters

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1. Akgün E, Javed MI, Lunzer MM, Powers MD, Sham YY, Watanabe Y, Portoghese PS. Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5). J Med Chem. 2015 Nov 12;58(21):8647–57.

2. Aldrich C. Introductory Editorial for ACS Infectious Diseases. ACS Infect Dis. 2015 Jan 9;1(1):1–2. 3. Aldrich C. Antibiotic Discovery for Mycobacteria. ACS Infect Dis. 2015 Dec 11;1(12):576–7. 4. Alverez C, Bulfer SL, Chakrasali R, Chimenti MS, Deshaies RJ, Green N, Kelly M, LaPorte MG, Lewis

TS, Liang M, Moore WJ, Neitz RJ, Peshkov VA, Walters MA, Zhang F, Arkin MR, Wipf P, Huryn DM. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway. ACS Med Chem Lett. 2015 Dec 22;7(2):182–7.

5. Anand A, Verma P, Singh AK, Kaushik S, Pandey R, Shi C, Kaur H, Chawla M, Elechalawar CK, Kumar D, Yang Y, Bhavesh NS, Banerjee R, Dash D, Singh A, Natarajan VT, Ojha AK, Aldrich CC, Gokhale RS. Polyketide Quinones Are Alternate Intermediate Electron Carriers during Mycobacterial Respiration in Oxygen-Deficient Niches. Mol Cell. 2015 Nov 19;60(4):637–50.

6. Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frederiksen M, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O’Hagan RC, Overington JP, Owen DR, Rosenberg SH, Ross R, Roth B, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ. Corrigendum: The Promise and Peril of Chemical Probes. Nat Chem Biol. 2015 Nov;11(11):887.

7. Basu D, Tian Y, Hui P, Bhandari J, Johnson RL, Mishra RK. Change in Expression of Vesicular Protein Synapsin II by Chronic Treatment with D2 Allosteric Modulator PAOPA. Peptides. 2015 Apr;66:58–62.

8. Beesu M, Caruso G, Salyer AC, Khetani KK, Sil D, Weerasinghe M, Tanji H, Ohto U, Shimizu T, David SA. Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity. J Med Chem. 2015 Oct 8;58(19):7833–49.

9. Bockman MR, Kalinda AS, Petrelli R, De la Mora-Rey T, Tiwari D, Liu F, Dawadi S, Nandakumar M, Rhee KY, Schnappinger D, Finzel BC, Aldrich CC. Targeting Mycobacterium tuberculosis Biotin Protein Ligase (MtBPL) with Nucleoside-Based Bisubstrate Adenylation Inhibitors. J Med Chem. 2015 Sep 24;58(18):7349–69.

10. Buonomo JA, Aldrich CC. Mitsunobu Reactions Catalytic in Phosphine and a Fully Catalytic System. Angew Chem Int Ed Engl. 2015 Oct 26;54(44):13041–4.

11. Casalena D, Nag PP, Park SW, Wilson D, Edwankar R, Johnston S, Le H, Schilling R, Bittker JA, Dandapani S, Munoz B, Dai R, Finzel BC, Schnappinger D, Aldrich C, Schreiber SL, Palmer M. Discovery of Small Molecule Probe that Shows Anti-tubercular Activity via Mtb BioA (DAPA Synthase) Enzyme Inhibition. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–2014 Apr 15 [updated 2015 Jan 16].

12. Chan JD, Agbedanu PN, Grab T, Zamanian M, Dosa PI, Day TA, Marchant JS. Ergot Alkaloids (Re)generate New Leads as Antiparasitics. PLoS Negl Trop Dis. 2015 Sep 14;9(9):e0004063.

13. Conway SJ, Woster PM, Shen JK, Georg GI, Wang S. Epigenetics: Novel Therapeutics Targeting Epigenetics. J Med Chem. 2015 Jan 22;58(2):523–4.

14. Dahlin JL, Chen X, Walters MA, Zhang Z. Histone-modifying Enzymes, Histone Modifications and Histone Chaperones in Nucleosome Assembly: Lessons Learned from Rtt109 Histone Acetyltransferases. Crit Rev Biochem Mol Biol. 2015 Jan-Feb;50(1):31–53.

15. Dahlin JL, Inglese J, Walters MA. Mitigating Risk in Academic Preclinical Drug Discovery. Nat Rev Drug Discov. 2015 Apr;14(4):279–94.

Publications

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16. Dahlin JL, Nissink JW, Francis S, Strasser JM, John K, Zhang Z, Walters MA. Post-HTS Case Report and Structural Alert: Promiscuous 4-aroyl-1,5-disubstituted-3-hydroxy-2H-pyrrol-2-one Actives Verified by ALARM NMR. Bioorg Med Chem Lett. 2015 Nov 1;25(21):4740–52.

17. Dahlin JL, Nissink JW, Strasser JM, Francis S, Higgins L, Zhou H, Zhang Z, Walters MA. PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-scavenging HTS. J Med Chem. 2015 Mar 12;58(5):2091–113.

18. Dai R, Geders TW, Liu F, Park SW, Schnappinger D, Aldrich CC, Finzel BC. Fragment-based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA. J Med Chem. 2015 Jul 9;58(13):5208–17.

19. Dawadi S, Viswanathan K, Boshoff HI, Barry CE 3rd, Aldrich CC. Investigation and Conformational Analysis of Fluorinated Nucleoside Antibiotics Targeting Siderophore Biosynthesis. J Org Chem. 2015 May 15;80(10):4835–50.

20. Ericson MD, Schnell SM, Freeman KT, Haskell-Luevano C. A Fragment of the Escherichia Coli ClpB Heat-shock Protein is a Micromolar Melanocortin 1 Receptor Agonist. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5306–8.

21. Ericson MD, Wilczynski A, Sorensen NB, Xiang Z, Haskell-Luevano C. Discovery of a β-Hairpin Octapeptide, c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], Mimetic of Agouti-Related Protein(87-132) [AGRP(87-132)] with Equipotent Mouse Melanocortin-4 Receptor (mMC4R) Antagonist Pharmacology. J Med Chem. 2015 Jun 11;58(11):4638–47.

22. Ferguson DM, Jacobson BA, Jay-Dixon J, Patel MR, Kratzke RA, Raza A. Targeting Topoisomerase II Activity in NSCLC with 9-Aminoacridine Derivatives. Anticancer Res. 2015 Oct;35(10):5211–7.

23. Fiers WD, Dodge GJ, Li Y, Smith JL, Fecik RA, Aldrich CC. Tylosin Polyketide Synthase Module 3: Stereospecificity, Stereoselectivity and Steady-state Kinetic Analysis of β-processing Domains via Diffusible, Synthetic Substrates. Chem Sci. 2015 Aug 14;6(8):5027–5033.

24. Ganapathi L, Van Haren S, Dowling DJ, Bergelson I, Shukla NM, Malladi SS, Balakrishna R, Tanji H, Ohto U, Shimizu T, David SA, Levy O. The Imidazoquinoline Toll-Like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes. PLoS One. 2015 Aug 14;10(8):e0134640.

25. Garrigan E, Belkin NS, Seydel F, Han Z, Carter J, McDuffie M, Morel L, Peck AB, Clare-Salzler MJ, Atkinson M, Wasserfall C, Davoodi-Semiromi A, Shi JD, Haskell-Luevano C, Yang LJ, Alexander JJ, Cdebaca A, Piliant T, Riggs C, Amick M, Litherland SA. Csf2 and Ptgs2 Epigenetic Dysregulation in Diabetes-prone Bicongenic B6.NODC11bxC1tb Mice. Genet Epigenet. 2015 Oct 11;7:5–17.

26. Garzón J, Herrero-Labrador R, Rodríguez-Muñoz M, Shah R, Vicente-Sánchez A, Wagner CR, Sánchez-Blázquez P. HINT1 Protein: A New Therapeutic Target to Enhance Opioid Antinociception and Block Mechanical Allodynia. Neuropharmacology. 2015 Feb;89:412–23.

27. Gruppi F, Hejazi L, Christov PP, Krishnamachari S, Turesky RJ, Rizzo CJ. Characterization of Nitrogen Mustard Formamidopyrimidine Adduct Formation of Bis(2-chloroethyl)ethylamine with Calf Thymus DNA and a Human Mammary Cancer Cell Line. Chem Res Toxicol. 2015 Sep 21;28(9):1850–60.

28. Gu X, Georg GI. Regioselective C5-alkylation and C5-methylcarbamate formation of 2,3-dihydro-4-pyridones and C3-alkylation and C3-methylcarbamate Formation of 4-(pyrrolidin-1-yl)furan-2(5H)-one. Tetrahedron Lett. 2015 Oct 21;56(43):5874–5877.

29. Guo J, Yonemori K, Le Marchand L, Turesky RJ. Method to Biomonitor the Cooked Meat Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Dyed Hair by Ultra-Performance Liquid Chromatography-Orbitrap High Resolution Multistage Mass Spectrometry. Anal Chem. 2015 Jun 16;87(12):5872–7.

30. Hexum JK, Becker CM, Kempema AM, Ohlfest JR, Largaespada DA, Harki DA. Parthenolide Prodrug LC-1 Slows Growth of Intracranial Glioma. Bioorg Med Chem Lett. 2015 Jun 15;25(12):2493–5.

31. Kempema AM, Widen JC, Hexum JK, Andrews TE, Wang D, Rathe SK, Meece FA, Noble KE, Sachs Z, Largaespada DA, Harki DA. Synthesis and Antileukemic Activities of C1-C10-modified Parthenolide

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Analogues. Bioorg Med Chem. 2015 Aug 1;23(15):4737–45. 32. Kerr JP, Robison P, Shi G, Bogush AI, Kempema AM, Hexum JK, Becerra N, Harki DA, Martin SS, Raiteri

R, Prosser BL, Ward CW. Detyrosinated Microtubules Modulate Mechanotransduction in Heart and Skeletal Muscle. Nat Commun. 2015 Oct 8;6:8526.

33. Kindrachuk KN, Aldrich CC. Going Viral. ACS Infect Dis. 2015 Sep 11;1(9):399. 34. Kirtane AR, Wong HL, Guru BR, Lis LG, Georg GI, Gurvich VJ, Panyam J. Reformulating Tylocrebrine

in Epidermal Growth Factor Receptor Targeted Polymeric Nanoparticles Improves Its Therapeutic Index. Mol Pharm. 2015 Aug 3;12(8):2912–23.

35. Konorev D, Koopmeiners JS, Tang Y, Franck Thompson EA, Jensen JA, Hatsukami DK, Turesky RJ. Measurement of the Heterocyclic Amines 2-Amino-9H-pyrido[2,3-b]indole and 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Urine: Effects of Cigarette Smoking. Chem Res Toxicol. 2015 Dec 21;28(12):2390–9.

36. Köse M, Purtas S, Güngör SA, Ceyhan G, Akgün E, McKee V. A novel Schiff base: Synthesis, Structural Characterisation and Comparative Sensor Studies for Metal Ion Detections. Spectrochim Acta A Mol Biomol Spectrosc. 2015 Feb 5;136 Pt C:1388–94.

37. Kotapati S, Esades A, Matter B, Le C, Tretyakova N. High Throughput HPLC-ESI(-)-MS/MS Methodology for Mercapturic Acid Metabolites of 1,3-butadiene: Biomarkers of Exposure and Bioactivation. Chem Biol Interact. 2015 Nov 5;241:23–31.

38. Kotapati S, Wickramaratne S, Esades A, Boldry EJ, Quirk Dorr D, Pence MG, Guengerich FP, Tretyakova NY. Polymerase Bypass of N(6)-Deoxyadenosine Adducts Derived from Epoxide Metabolites of 1,3-Butadiene. Chem Res Toxicol. 2015 Jul 20;28(7):1496–507.

39. Kurbanov EK, Chiu TL, Solberg J, Francis S, Maize KM, Fernandez J, Johnson RL, Hawkinson JE, Walters MA, Finzel BC, Amin EA. Probing the S2’ Subsite of the Anthrax Toxin Lethal Factor Using Novel N-Alkylated Hydroxamates. J Med Chem. 2015 Nov 12;58(21):8723–33.

40. Li W, Georg GI. A Concise Formal Total Synthesis of Lactimidomycin. Chem Commun (Camb). 2015 May 21;51(41):8634–6.

41. Olesen SH, Ingles DJ, Zhu JY, Martin MP, Betzi S, Georg GI, Tash JS, Schönbrunn E. Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2. Molecules. 2015 Jan 19;20(1):1643–60.

42. Li W, Schneider CM, Georg GI. Synthesis of Strained 1,3-Diene Macrocycles via Copper-Mediated Castro-Stephens Coupling/Alkyne Reduction Tandem Reactions. Org Lett. 2015 Aug 7;17(15):3902–5.

43. Li Y, Dodge GJ, Fiers WD, Fecik RA, Smith JL, Aldrich CC. Functional Characterization of a Dehydratase Domain from the Pikromycin Polyketide Synthase. J Am Chem Soc. 2015 Jun 10;137(22):7003–6.

44. Liu Z, Liu F, Aldrich CC. Stereocontrolled Synthesis of a Potential Transition-State Inhibitor of the Salicylate Synthase MbtI from Mycobacterium tuberculosis. J Org Chem. 2015 Jul 2;80(13):6545–52.

45. Ma B, Villalta PW, Zarth AT, Kotandeniya D, Upadhyaya P, Stepanov I, Hecht SS. Comprehensive High-Resolution Mass Spectrometric Analysis of DNA Phosphate Adducts Formed by the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Res Toxicol. 2015 Nov 16;28(11):2151–9.

46. Maize KM, Kurbanov EK, Johnson RL, Amin EA, Finzel BC. Ligand-induced Expansion of the S1’ Site in the Anthrax Toxin Lethal Factor. FEBS Lett. 2015 Dec 21;589(24 Pt B):3836–41

47. Makowska-Grzyska M, Kim Y, Gorla SK, Wei Y, Mandapati K, Zhang M, Maltseva N, Modi G, Boshoff HI, Gu M, Aldrich C, Cuny GD, Hedstrom L, Joachimiak A. Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds. PLoS One. 2015 Oct 6;10(10):e0138976.

48. McFaline-Figueroa JL, Braun CJ, Stanciu M, Nagel ZD, Mazzucato P, Sangaraju D, Cerniauskas E, Barford K, Vargas A, Chen Y, Tretyakova N, Lees JA, Hemann MT, White FM, Samson LD. Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to

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Temozolomide. Cancer Res. 2015 Aug 1;75(15):3127–38. 49. Monien BH, Schumacher F, Herrmann K, Glatt H, Turesky RJ, Chesné C. Simultaneous Detection of

Multiple DNA Adducts in Human Lung Samples by Isotope-dilution UPLC-MS/MS. Anal Chem. 2015 Jan 6;87(1):641–8.

50. Murray BC, Peterson MT, Fecik RA. Chemistry and Biology of Tubulysins: Antimitotic Tetrapeptides with Activity against Drug Resistant Cancers. Nat Prod Rep. 2015 May;32(5):654–62.

51. Nelson KM, Viswanathan K, Dawadi S, Duckworth BP, Boshoff HI, Barry CE 3rd, Aldrich CC. Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis Inhibitors for Mycobacterium tuberculosis. J Med Chem. 2015 Jul 23;58(14):5459–75.

52. Park SW, Casalena DE, Wilson DJ, Dai R, Nag PP, Liu F, Boyce JP, Bittker JA, Schreiber SL, Finzel BC, Schnappinger D, Aldrich CC. Target-based Identification of Whole-cell Active Inhibitors of Biotin Biosynthesis in Mycobacterium tuberculosis. Chem Biol. 2015 Jan 22;22(1):76–86.

53. Pathak KV, Bellamri M, Wang Y, Langouët S, Turesky RJ. 2-Amino-9H-pyrido[2,3-b]indole (AαC) Adducts and Thiol Oxidation of Serum Albumin as Potential Biomarkers of Tobacco Smoke. J Biol Chem. 2015 Jun 26;290(26):16304–18.

54. Patil S, Lis LG, Schumacher RJ, Norris BJ, Morgan ML, Cuellar RA, Blazar BR, Suryanarayanan R, Gurvich VJ, Georg GI. Phosphonooxymethyl Prodrug of Triptolide: Synthesis, Physicochemical Characterization, and Efficacy in Human Colon Adenocarcinoma and Ovarian Cancer Xenografts. J Med Chem. 2015 Dec 10;58(23):9334–44.

55. Polepally AR, Remmel RP, Brundage RC, Leppik IE, Rarick JO, Ramsay RE, Birnbaum AK. Steady-state Pharmacokinetics and Bioavailability of Immediate-release and Extended-release Formulations of Lamotrigine in Elderly Epilepsy Patients: Use of Stable Isotope Methodology. J Clin Pharmacol. 2015 Oct;55(10):1101–8.

56. Pulk RA, Schladt DS, Oetting WS, Guan W, Israni AK, Matas AJ, Remmel RP, Jacobson PA; DeKAF Investigators. Multigene Predictors of Tacrolimus Exposure in Kidney Transplant Recipients. Pharmacogenomics. 2015 Jul;16(8):841–54.

57. Richards C, Albin JS, Demir Ö, Shaban NM, Luengas EM, Land AM, Anderson BD, Holten JR, Anderson JS, Harki DA, Amaro RE, Harris RS. The Binding Interface between Human APOBEC3F and HIV-1 Vif Elucidated by Genetic and Computational Approaches. Cell Rep. 2015 Dec 1;13(9):1781–8.

58. Roy Chowdhury U, Bahler CK, Holman BH, Dosa PI, Fautsch MP. Correction: Ocular Hypotensive Effects of the ATP-Sensitive Potassium Channel Opener Cromakalim in Human and Murine Experimental Model Systems. PLoS One. 2015 Dec 15;10(12):e0144791.

59. Shen J, Vallera DA, Wagner CR. Prosthetic Antigen Receptors. J Am Chem Soc. 2015 Aug 19;137(32):10108–11.

60. Shields-Cutler RR, Crowley JR, Hung CS, Stapleton AE, Aldrich CC, Marschall J, Henderson JP. Human Urinary Composition Controls Antibacterial Activity of Siderocalin. J Biol Chem. 2015 Jun 26;290(26):15949–60.

61. Siegel RA, Kapoor M, Cheryala N, Georg GI, Cloyd JC. Water-soluble Benzodiazepine Prodrug/enzyme Combinations for Intranasal Rescue Therapies. Epilepsy Behav. 2015 Aug;49:347–50.

62. Singh A, Tala SR, Flores V, Freeman K, Haskell-Luevano C. Synthesis and Pharmacology of α/β(3)-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence. ACS Med Chem Lett. 2015 Apr 8;6(5):568–72.

63. Srivastava S, Chaudhary S, Thukral L, Shi C, Gupta RD, Gupta R, Priyadarshan K, Vats A, Haque AS, Sankaranarayanan R, Natarajan VT, Sharma R, Aldrich CC, Gokhale RS. Unsaturated Lipid Assimilation by Mycobacteria Requires Auxiliary cis-trans Enoyl CoA Isomerase. Chem Biol. 2015 Dec 17;22(12):1577–87.

64. Syeda SS, Jakkaraj S, Georg GI. Scalable Syntheses of the BET Bromodomain Inhibitor JQ1. Tetrahedron

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Lett. 2015 Jun 3;56(23):3354–3457.65. Tala SR, Schnell SM, Haskell-Luevano C. Microwave-assisted Solid-phase Synthesis of Side-chain to

Side-chain Lactam-bridge Cyclic Peptides. Bioorg Med Chem Lett. 2015 Dec 15;25(24):5708–11. 66. Tidey JP, O’Connor AE, Markevich A, Bichoutskaia E, Cavan JJ, Lawrance GA, Wong HL, McMaster

J, Schröder M, Blake AJ. Epitaxial Retrieval of a Disappearing Polymorph. Cryst Growth Des. 2015 Jan 7;15(1):115–123.

67. Tretyakova NY, Groehler, A 4th, Ji S. DNA-Protein Cross-Links: Formation, Structural Identities, and Biological Outcomes. Acc Chem Res. 2015 Jun 16;48(6):1631–44.

68. Turesky RJ, Konorev D, Fan X, Tang Y, Yao L, Ding X, Xie F, Zhu Y, Zhang QY. Effect of Cytochrome P450 Reductase Deficiency on 2-Amino-9H-pyrido[2,3-b]indole Metabolism and DNA Adduct Formation in Liver and Extrahepatic Tissues of Mice. Chem Res Toxicol. 2015 Dec 21;28(12):2400–10.

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Photo Captionscover Weaver-Densford Hall Buildingp.ii Gunda Georgp. 1 top Sara Coulup; Alex Strom; Marilyn Speedie bottom Stephanie Breunig; Sunil Davidp. 2 top Barry Finzel; Elizabeth Ambrosep. 3 Fall 2015 ITDD faculty and staff: Shameem Sultana, Sara Coulup, Kristen John, Rawle Francis, Kristen Stoltz, Matthew Cuellar, Ryan Harding, Peter Dosa, Jonathan Solberg, Erick Carlson, Jiewei Jiang, Shams Ul-Mahmood, Xianghong Guan, Zhenyuan Miao, Narsihmulu Cheryala (top row) / Tim Ward, Jillian Kyzer, David Huang, Henry Wong, Michael Walters, Kathryn Nelson, Andi Wisniewski, Jessica Strasser, Gurpreet Singh, Defeng Tian (middle row) / Soma Maitra, Amy Holth, Rebecca Cuellar, Gunda Georg, Vadim Gurvich, Lev Lis, Kwon Ho Hongp. 4 right side Gunda Georg; Philip Portoghese; David Ferguson; Elizabeth Ambrose; Courtney Aldrich middle Fall 2015 Faculty Members: Siddath Kumarapperuma, Elizabeth Ambrose, Sunil David, Carrie Haskell-Luevano, David Ferguson, Chris Xing, Jon Hawkinson (top row) / Vadim Gurvich, Michael Walters, Gunda Georg, Carston Wagner, Peter Dosa, Earl Dunham (bottom row)p. 5 Gunda Georg; Stephen Hecht; Michael Walters; Jessica Strasser; Vadim Gurvichp. 6 top Bryan Roth; Craig Lindsley; Adam Zarth bottom Frank Raushel; Kim Janda; Joel Barrish; Barbara Timmermannp. 7 New graduate students Amanda Degner, John Schultz, Dmitri Konorev, Corey Geehan, Malcolm Cole, Anand Divakaran, Connor McDermott, Ellie Hofer, Kathryn Schlasner, William McCuep. 8 top Elbek Kurbanov; Adam Zarth; Kimberly Maize; Joseph Buonomo; Sara Coulup bottom Stephanie Breunig; Aniekan Okon; Clifford Csizmar; John Widen; Laura Burnesp. 9 McNamara wall of booksp. 11 Bo Zhou, 717 Delaware; Sara Coulup, 717 Delaware; John Widen, CCRB; Jill Kyzer, 717 Delawarep. 12 top Katlyn Fleming bottom Sara Coulup, 717 Delaware; Bo Zhou, CCRB NMR; Katlyn Fleming, 717 Delawarep. 13 Alex Strom, CCRB; Ozgun Kilic, CCRB; Elbek Kurbanov, 717 Delaware

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