Colchicine glycorandomization influences cytotoxicity and mechanism of action
Colchicine glycorandomization influences cytotoxicity and mechanism of action
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DOI：
10.1021/ja064686s
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发表时间：
2006-11-08
影响因子：
15
通讯作者：
Thorson, Jon S.
中科院分区：
文献类型：
--
作者：
Ahmed, Aqeel;Peters, Noel R.;Thorson, Jon S.
反应的70个未保护的，二硫键官能化的游离还原糖与甲氧胺附加秋水仙碱导致的58个成员的糖随机化库的生产。高通量细胞毒性测定揭示了糖基化调节特异性和效力。还鉴定了文库成员，其与亲本天然产物（去稳定剂）不同，以类似于紫杉醇的方式稳定体外微管蛋白聚合。这项研究强调了一个简单的扩展neoglycorandomization对含胺支架和糖基化非糖基化天然产物的潜在好处。
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.