TY - BOOK ID - 8134998 TI - Tubulin-binding agents : synthetic, structural, and mechanistic insights AU - Altmann, Karl-Heinz. AU - Carlomagno, Teresa. PY - 2009 SN - 3540690360 9786613560643 1280382732 3540690395 9783540690368 PB - Berlin ; New York : Springer, DB - UniCat KW - Tubulins KW - Stabilizing agents KW - Microtubules KW - Chemistry KW - Tubulin KW - Nerve Tissue Proteins KW - Microtubule Proteins KW - Natural Science Disciplines KW - Cytoskeleton KW - Proteins KW - Cytoplasmic Structures KW - Disciplines and Occupations KW - Cytoskeletal Proteins KW - Biopolymers KW - Amino Acids, Peptides, and Proteins KW - Cytoplasm KW - Polymers KW - Macromolecular Substances KW - Chemicals and Drugs KW - Intracellular Space KW - Cellular Structures KW - Cells KW - Anatomy KW - Animal Biochemistry KW - Pharmacy, Therapeutics, & Pharmacology KW - Chemical Engineering KW - Chemical & Materials Engineering KW - Health & Biological Sciences KW - Human Anatomy & Physiology KW - Engineering & Applied Sciences KW - Microtubules. KW - Stabilizing agents. KW - Tubulins. KW - Agents, Stabilizing KW - Stabilizers (Chemistry) KW - Cytotubules KW - Microtubule proteins KW - Chemistry. KW - Cancer research. KW - Analytical chemistry. KW - Organic chemistry. KW - Medicinal chemistry. KW - Biochemistry. KW - Medicinal Chemistry. KW - Biochemistry, general. KW - Cancer Research. KW - Organic Chemistry. KW - Analytical Chemistry. KW - Chemicals KW - Cell organelles KW - Oncology. KW - Chemistry, Organic. KW - Analytical biochemistry. KW - Analytic biochemistry KW - Biochemistry KW - Chemistry, Analytic KW - Organic chemistry KW - Tumors KW - Biological chemistry KW - Chemical composition of organisms KW - Organisms KW - Physiological chemistry KW - Biology KW - Medical sciences KW - Composition KW - Bioanalytic chemistry KW - Bioanalytical chemistry KW - Analytical chemistry KW - Analysis, Chemical KW - Analytic chemistry KW - Chemical analysis KW - Cancer research KW - Chemistry, Medical and pharmaceutical KW - Chemistry, Pharmaceutical KW - Drug chemistry KW - Drugs KW - Medical chemistry KW - Medicinal chemistry KW - Pharmacochemistry UR - https://www.unicat.be/uniCat?func=search&query=sysid:8134998 AB - 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 comparison of the different approaches. The third chapter describes a comprehensive study of the mechanisms of activity of microtubules stabilizing drugs. Thermodynamic, kinetic, structural and functional 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. ER -