Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues.
[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.
Metaferia
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BB
Departments of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Hoch
J
J
Glass
T E
TE
Bane
S L
SL
Chatterjee
S K
SK
Snyder
J P
JP
Lakdawala
A
A
Cornett
B
B
Kingston
D G
DG
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
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D014404:Tubulin; D017239:Paclitaxel