Chemical tagging of a drug target using 5-sulfonyl tetrazole |
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Authors: | Satsuki Otsuki Shinichi Nishimura Hisae Takabatake Kozue Nakajima Yasuaki Takasu Toru Yagura Yuki Sakai Akira Hattori Hideaki Kakeya |
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Institution: | Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan |
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Abstract: | 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. |
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