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Vehiculization of two novel metal complexes to cancer cells Andreu Paytuví Gallart

Vehiculization of two novel metal complexes to cancer cells

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Page 1: Vehiculization of two novel metal complexes to cancer cells

Vehiculization of two novel metal complexes to cancer cells

Andreu Paytuví Gallart

Page 2: Vehiculization of two novel metal complexes to cancer cells

Introduction: cancer

Figure references: Friedrich Marks. Cellular Signal Processing: An Introduction to the Molecular Mechanisms of Signal Transduction. Taylor & Francis Ltd. (2008).

Page 3: Vehiculization of two novel metal complexes to cancer cells

Introduction: treatments

Novel metal complexes

Figure references: Kartalou, Maria; Essigmann, John M . Recognition of cisplatin adducts by cellular proteins. Mutat. Res-Fun. Mol. M. 478, 1–21 (2001).

Page 4: Vehiculization of two novel metal complexes to cancer cells

Introduction: bombesin

Bombesin:

Figure references: Robinson, Clifford R. Reduce, reuse, and recycle. Nature Biotechnology 20, 879 - 880 (2002).

Page 5: Vehiculization of two novel metal complexes to cancer cells

Objectives

• Synthesis of bombesin analogs

• Attaching either complex K, complex CA323, or 5(6)-

carboxyfluorescein to bombesin analogs.

• DNA binding studies of complexes K and CA323.

Page 6: Vehiculization of two novel metal complexes to cancer cells

Results: Design of bombesin analogs

Pyr Met14

Page 7: Vehiculization of two novel metal complexes to cancer cells

Results: Synthesis of bombesin analogues

Page 8: Vehiculization of two novel metal complexes to cancer cells

Results: Synthesis of bombesin analogues incorporating the complex CA323

APG-6-CA323 APG-9-CA323 APG-9-NLS-CA323

Page 9: Vehiculization of two novel metal complexes to cancer cells

Results: Synthesis of bombesin analogues incorporating the complex CA323

Page 10: Vehiculization of two novel metal complexes to cancer cells

Results: Synthesis of bombesin analogues incorporating the complex CA323

Page 11: Vehiculization of two novel metal complexes to cancer cells

Results: Synthesis of bombesin analogues incorporating the complex K

APG-9-(Complex K) (93% purity) APG-9-NLS-(Complex K) (83% purity)

Page 12: Vehiculization of two novel metal complexes to cancer cells

Results: Synthesis of 5(6)-carboxyfluorescein-labeled bombesin analogs

Page 13: Vehiculization of two novel metal complexes to cancer cells

Results: Attempts for the synthesis of 5(6)-carboxyfluorescein-labeled bombesin analogs containing the metal complex CA323

None of them were obtained.

Page 14: Vehiculization of two novel metal complexes to cancer cells

Results: binding studies Se

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Page 15: Vehiculization of two novel metal complexes to cancer cells

Summary

• Bombesin analogs APG-6, APG-9, APG-9-Lys and APG-9-NLS.

– Synthesized in good to excellent purity (79-100%).

• Bombesin analog incorporating complex CA323, APG-9-(CA323).

– Synthesized in 57% purity.

• Bombesin analogs incorporating complex K, APG-9-(Complex K) and APG-9-NLS-(Complex K).

– Synthesized in 93% and 83% respectively.

• 5(6)-carboxyfluorescein-labeled bombesin analogs APG-9-CF-Lys and APG-9-Lys(CF).

– Synthesized in 69% and 100% purity, respectively.

• Neither complex K nor CA323 showed remarkable DNA interaction under our working conditions.