Colchicine glycorandomization influences cytotoxicity and mechanism of action

被引：74

作者：

Ahmed, Aqeel

Peters, Noel R.

Fitzgeraldo, Megan K.

Watson, James A., Jr.

Hoffmann, F. Michael

Thorson, Jon S. ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Pharm, Pharmaceut Sci Div, Madison, WI 53705 USA

[2] Keck Univ Wisconsin, Ctr Comprehens Canc, Small Mol Screening Facil, Madison, WI 53705 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 44期

关键词：

D O I：

10.1021/ja064686s

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The reaction of 70 unprotected, diversely functionalized free reducing sugars with methoxyamine-appended colchicine led to the production of a 58-member glycorandomized library. High-throughput cytotoxicity assays revealed glycosylation to modulate specificity and potency. Library members were also identified which, unlike the parent natural product (a destabilizer), stabilized in vitro tubulin polymerization in a manner similar to taxol. This study highlights a simple extension of neoglycorandomization toward amine-bearing scaffolds and the potential benefit of glycosylating nonglycosylated natural products. Copyright © 2006 American Chemical Society.

引用

页码：14224 / 14225

页数：2

共 36 条

[1] Substrate specificity of NovM: Implications for novobiocin biosynthesis and glycorandomization [J].