Abstract
[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Binding Sites
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Crystallography, X-Ray
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Cyclization
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Humans
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Indicators and Reagents
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Models, Molecular
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Molecular Conformation
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Paclitaxel / analogs & derivatives
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Paclitaxel / chemical synthesis*
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Paclitaxel / pharmacology*
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Tubulin / chemistry
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents, Phytogenic
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Indicators and Reagents
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Tubulin
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Paclitaxel