vehiculization of two novel metal complexes to cancer cells
TRANSCRIPT
Vehiculization of two novel metal complexes to cancer cells
Andreu Paytuví Gallart
Introduction: cancer
Figure references: Friedrich Marks. Cellular Signal Processing: An Introduction to the Molecular Mechanisms of Signal Transduction. Taylor & Francis Ltd. (2008).
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).
Introduction: bombesin
Bombesin:
Figure references: Robinson, Clifford R. Reduce, reuse, and recycle. Nature Biotechnology 20, 879 - 880 (2002).
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.
Results: Design of bombesin analogs
Pyr Met14
Results: Synthesis of bombesin analogues
Results: Synthesis of bombesin analogues incorporating the complex CA323
APG-6-CA323 APG-9-CA323 APG-9-NLS-CA323
Results: Synthesis of bombesin analogues incorporating the complex CA323
Results: Synthesis of bombesin analogues incorporating the complex CA323
Results: Synthesis of bombesin analogues incorporating the complex K
APG-9-(Complex K) (93% purity) APG-9-NLS-(Complex K) (83% purity)
Results: Synthesis of 5(6)-carboxyfluorescein-labeled bombesin analogs
Results: Attempts for the synthesis of 5(6)-carboxyfluorescein-labeled bombesin analogs containing the metal complex CA323
None of them were obtained.
Results: binding studies Se
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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.