1. Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues.
- Author
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Metaferia BB, Hoch J, Glass TE, Bane SL, Chatterjee SK, Snyder JP, Lakdawala A, Cornett B, and Kingston DG
- Subjects
- Binding Sites, Crystallography, X-Ray, Cyclization, Humans, Indicators and Reagents, Models, Molecular, Molecular Conformation, Paclitaxel analogs & derivatives, Tubulin chemistry, Tumor Cells, Cultured, Antineoplastic Agents, Phytogenic chemical synthesis, Antineoplastic Agents, Phytogenic pharmacology, Paclitaxel chemical synthesis, Paclitaxel pharmacology
- 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.
- Published
- 2001
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