Design, synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP
| Autor: | John C. Reed, Pooi San Lee, Kate Welsh, Kristiina Vuori, Darren Finlay, Nicholas D. P. Cosford, Palaniyandi Ravanan, Peter D. Mace, Marcos González-López, Robert Ardecky, Stefan J. Riedl, Santhi Ganji |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cell Survival
Peptidomimetic Clinical Biochemistry Pharmaceutical Science X-Linked Inhibitor of Apoptosis Protein Plasma protein binding Inhibitor of apoptosis Biochemistry Article TNF-Related Apoptosis-Inducing Ligand Structure-Activity Relationship Biomimetic Materials Cell Line Tumor Drug Discovery Humans Structure–activity relationship Molecular Biology Binding Sites Chemistry Organic Chemistry Rational design Ligand (biochemistry) Protein Structure Tertiary XIAP Molecular Docking Simulation Drug Resistance Neoplasm Apoptosis Drug Design Cancer research Molecular Medicine Oligopeptides Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 23:4253-4257 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2013.04.096 |
| Popis: | We recently reported the systematic ligand-based rational design and synthesis of monovalent Smac mimetics that bind preferentially to the BIR2 domain of the anti-apoptotic protein XIAP. Expanded structure–activity relationship (SAR) studies around these peptidomimetics led to compounds with significantly improved selectivity (>60-fold) for the BIR2 domain versus the BIR3 domain of XIAP. The potent and highly selective IAP antagonist 8q (ML183) sensitized TRAIL-resistant prostate cancer cells to apoptotic cell death, highlighting the merit of this probe compound as a valuable tool to investigate the biology of XIAP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect