Design and Synthesis of Activity-Based Probes and Inhibitors for Bleomycin Hydrolase
作者： Wouter A. van der Linden , Ehud Segal , Matthew A. Child , Anna Byzia , Marcin Drąg
DOI: 10.1016/J.CHEMBIOL.2015.07.010
关键词:
摘要: Bleomycin hydrolase (BLMH) is a neutral cysteine aminopeptidase that has been ascribed roles in many physiological and pathological processes, yet its primary biological function remains enigmatic. In this work, we describe the results of screening library fluorogenic substrates to identify non-natural amino acids are optimally recognized by BLMH. This screen identified several with kcat/KM values substantially improved over previously reported for enzyme. The substrate sequences were used design activity-based probes showed potent labeling recombinant BLMH as well endogenously expressed cell extracts, intact cells. Importantly, inhibitors able fully inhibit endogenous activity These will be valuable new reagents study cellular animal models human diseases where likely involved.
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