Chemical tagging of a drug target using 5-sulfonyl tetrazole
Chemical tagging of a drug target using 5-sulfonyl tetrazole
复制标题
使用 5-磺酰四唑对药物靶标进行化学标记
DOI：
10.1016/j.bmcl.2013.01.092
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发表时间：
2013
影响因子：
2.7
通讯作者：
& Kakeya H
中科院分区：
文献类型：
--
作者：
Otsuki S;Nishimura S;Takabatake H;Nakajima K;Takasu Y;Yagura T;Sakai Y;Hattori A;& Kakeya H
不可逆修饰是鉴定生物活性小分子细胞受体的最有前途的策略之一。在这里，我们报告说，受体蛋白可以使用5-磺酰基四唑探针化学标记。5-磺酰基四唑易于接受硫醇基团的亲核攻击，而5-亚磺酰基四唑不。将这些官能团引入天然产物的探针分子中。环孢菌素A是一种由微生物产生的免疫抑制剂，经衍生化后具有5-磺酰基四唑和一个标签基团，这使得环孢菌素A的细胞受体亲环素A能够被化学标记。含有5-亚磺酰基四唑的环孢菌素A衍生物不能标记亲环素A。该技术将允许有效鉴定生物活性小分子的细胞受体。
Irreversible modification is one of the most promising strategies to identify cellular receptors of bioactive small molecules. Here we report that receptor proteins can be chemically tagged using a 5-sulfonyl tetrazole probe. 5-Sulfonyl tetrazole easily accepted nucleophilic attack of thiol groups, while 5-sulfinyl tetrazole did not. These functional groups were introduced into probe molecules of a natural product. Cyclosporine A, an immunosuppressant produced by a microbe, was derivatized to possess 5-sulfonyl tetrazole and a tag group, which enabled chemical tagging of cyclophilin A, the cellular receptor of cyclosporine A. Cyclosporine A derivative possessing 5-sulfinyl tetrazole could not tag cyclophilin A. This technique will allow efficient identification of cellular receptors of bioactive small molecules.