title: Bridging converts a noncytotoxic nor-paclitaxel derivative to a cytotoxic analogue by constraining it to the T-Taxol conformation.
abstract: The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially noncytotoxic, the bridged analogue 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.
authors.affiliation: Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: Shoubin
authors.initials: S
authors.lastname: Tang
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Peggy
authors.initials: P
authors.lastname: Brodie
authors.forename: Susan
authors.initials: S
authors.lastname: Bane
authors.forename: Rudravajhala
authors.initials: R
authors.lastname: Ravindra
authors.forename: Shubhada
authors.initials: S
authors.lastname: Sharma
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
authors.forename: David G I
authors.initials: DG
authors.lastname: Kingston
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D008958:Models, Molecular; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D014404:Tubulin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D017239:Paclitaxel