title: Chemical tagging of a drug target using 5-sulfonyl tetrazole.
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.
authors: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors: Satsuki
authors: S
authors: Otsuki
authors: Shinichi
authors: S
authors: Nishimura
authors: Hisae
authors: H
authors: Takabatake
authors: Kozue
authors: K
authors: Nakajima
authors: Yasuaki
authors: Y
authors: Takasu
authors: Toru
authors: T
authors: Yagura
authors: Yuki
authors: Y
authors: Sakai
authors: Akira
authors: A
authors: Hattori
authors: Hideaki
authors: H
authors: Kakeya
mesh_terms: D021984:Cyclophilin A / Q000737:chemistry* / Q000378:metabolism; D016572:Cyclosporine / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D013777:Tetrazoles / Q000737:chemistry*
chemical_list: D008024:Ligands; D013777:Tetrazoles; C045574:1H-tetrazole; D016572:Cyclosporine; D021984:Cyclophilin A