以膦酸酯和次膦酸酯为弹头的靶向弗林蛋白酶的基于活性的探针。

Furin-targeting activity-based probes with phosphonate and phosphinate esters as warheads.

作者信息

Ji Shanping, Verhelst Steven H L

机构信息

Laboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, 3000 Leuven, Belgium.

AG Chemical Proteomics, Leibniz Institute for Analytical Sciences - ISAS, 44227 Dortmund, Germany.

出版信息

Org Biomol Chem. 2023 Aug 16;21(32):6498-6502. doi: 10.1039/d3ob00948c.

DOI:10.1039/d3ob00948c

PMID:37530461

Abstract

Activity-based probes (ABPs) are covalent chemical tools that are widely used to target proteases in chemical biology. Here, we report a series of novel ABPs for the serine protease furin with phosphonate and phosphinate esters as reactive electrophiles. We show that these probes covalently label furin and have nanomolar potencies, because of proposed interactions with the different recognition pockets around the active site of furin.

摘要

基于活性的探针（ABPs）是共价化学工具，在化学生物学中广泛用于靶向蛋白酶。在此，我们报道了一系列以膦酸酯和次膦酸酯作为反应性亲电试剂的新型针对丝氨酸蛋白酶弗林蛋白酶的ABPs。我们表明，由于与弗林蛋白酶活性位点周围不同识别口袋的假定相互作用，这些探针可共价标记弗林蛋白酶且具有纳摩尔级别的效力。