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Tubulin-Binding Agents

Synthetic, Structural and Mechanistic Insights

  • Book
  • © 2009

Overview

Editors:
  1. Teresa Carlomagno

    1. Laboratory (EMBL), European Molecular Biology, Heidelberg, Germany

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  • This series presents critical reviews of the present position and future trends in modern chemical research
  • Short and concise reports on chemistry, each written by the world renowned experts
  • Still valid and useful after 5 or 10 years
  • More information as well as the electronic version of the whole content available at: springerlink.com
  • Includes supplementary material: sn.pub/extras

Part of the book series: Topics in Current Chemistry (TOPCURRCHEM, volume 286)

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Table of contents (7 chapters)

  1. Front Matter

    Pages i-xi
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  2. Macrolide-Based Microtubule-Stabilizing Agents – Chemistry and Structure–Activity Relationships

    • B. Pfeiffer, C.N. Kuzniewski, C. Wullschleger, K.-H. Altmann
    Pages 1-72

  3. The Chemical Synthesis of Discodermolide

    • I. Paterson, G. J. Florence
    Pages 73-119

  4. The Interaction of Microtubules with Stabilizers Characterized at Biochemical and Structural Levels

    • J. F. Díaz, J. M. Andreu, J. Jiménez-Barbero
    Pages 121-149

  5. The Tubulin Binding Mode of MT Stabilizing and Destabilizing Agents Studied by NMR

    • Víctor M. Sánchez-Pedregal, Christian Griesinger
    Pages 151-208

  6. The Tubulin Binding Mode of Microtubule Stabilizing Agents Studied by Electron Crystallography

    • James H. Nettles, Kenneth H. Downing
    Pages 209-257

  7. Microtubule-Destabilizing Agents: Structural and Mechanistic Insights from the Interaction of Colchicine and Vinblastine with Tubulin

    • B. Gigant, A. Cormier, A. Dorléans, R. B. G. Ravelli, M. Knossow
    Pages 259-278

  8. Molecular Modeling Approaches to Study the Binding Mode on Tubulin of Microtubule Destabilizing and Stabilizing Agents

    • Maurizio Botta, Stefano Forli, Matteo Magnani, Fabrizio Manetti
    Pages 279-328

  9. Back Matter

    Pages 329-331
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About this book

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.

Editors and Affiliations

  • Laboratory (EMBL), European Molecular Biology, Heidelberg, Germany

    Teresa Carlomagno

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