title: Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues.
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.
authors.affiliation: Departments of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Metaferia
authors.forename: J
authors.initials: J
authors.lastname: Hoch
authors.forename: T E
authors.initials: TE
authors.lastname: Glass
authors.forename: S L
authors.initials: SL
authors.lastname: Bane
authors.forename: S K
authors.initials: SK
authors.lastname: Chatterjee
authors.forename: J P
authors.initials: JP
authors.lastname: Snyder
authors.forename: A
authors.initials: A
authors.lastname: Lakdawala
authors.forename: B
authors.initials: B
authors.lastname: Cornett
authors.forename: D G
authors.initials: DG
authors.lastname: Kingston
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003500:Cyclization; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D014404:Tubulin; D017239:Paclitaxel