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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.

Tubulins --- Stabilizing agents --- Microtubules

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Epothilones have received unusual attention over the past ten years. They are novel antitumor drugs which very much like their predecessor paclitaxel (Taxol) act via microtubule stabilization. In comparison to paclitaxel and a number of alternative drugs with a similar mode of bioaction (e.g. laulimalide, eleutherobin, peluroside, discodermolide) the epothilones have significant advantages, above all very high activity in the nanomolar range and low susceptibility towards multidrug resistance. Epothilone B and several derivatives thereof are in phase I-III clinical trials; one of them (ixabepilone, BMS) is already on the market, others are supposed to appear on the market in the near future. All naturally occurring epothilones have been isolated from Sorangium cellulosum; their antitumor action is traced back to the stabilization of microtubules. In consequence, the formation of the mitototic spindle is prohibited and the cell undergoes apoptosis.

Organic chemistry --- Clinical chemistry --- Engineering sciences. Technology --- Biotechnology --- tumoren --- klinische chemie --- medische chemie --- organische chemie --- BIT (biochemische ingenieurstechnieken) --- biochemie --- biotechnologie --- ingenieurswetenschappen