[Topics in Current Chemistry] Tubulin-Binding Agents Volume 286 || Microtubule-Destabilizing Agents: Structural and Mechanistic Insights from the Interaction of Colchicine and Vinblastine with Tubulin
✍ Scribed by Carlomagno, Teresa
- Book ID
- 121712478
- Publisher
- Springer Berlin Heidelberg
- Year
- 2008
- Tongue
- German
- Weight
- 483 KB
- Edition
- 2009
- Category
- Article
- ISBN
- 3540690395
No coin nor oath required. For personal study only.
✦ Synopsis
reviews. The SAR data are discussed in light of the structural information available for each agent. The second chapter focuses on the total synthesis of the marine sponge-derived polyketide discodermolide. A comprehensive survey of the synthetic chemistry efforts of several groups over a 14-year period is provided together with a compa- son of the different approaches. The third chapter describes a comprehensive study of the mechanisms of activity of microtubules stabilizing drugs. Thermodynamic, kinetic, structural and fu- tional data on microtubules stabilizing drugs are discussed in an interdisciplinary manner to generate a “time-resolved” picture of the interaction of the drugs with different tubulin forms. The fourth and fifth chapters review the efforts and achievements made in the characterization of the structure of the complexes of tubulin with microtubules stabilizing agents by NMR (Chapter 4) and EM (Chapter 5). Especially evident is the discrepancy of the results obtained for epothilones, where the two techniques deliver radically different structures of the bound drug. Both NMR and EM models are, however, able to explain a consistent set of SAR data. The authors of the two chapters discuss critically the advantages and limitations of each methodology.