Synthesis and biological evaluation of novel irreversible serine protease inhibitors using amino acid based sulfonyl fluorides as an electrophilic trap

被引：43

作者：

Brouwer, Arwin J. ^{[1
]}

Ceylan, Tarik ^{[1
]}

Jonker, Anika M. ^{[1
]}

van der Linden, Tima ^{[1
]}

Liskamp, Rob M. J. ^{[1
]}

机构：

[1] Univ Utrecht, Dept Med Chem & Chem Biol, Utrecht Inst Pharmaceut Sci, Fac Sci, NL-3508 TB Utrecht, Netherlands

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 07期

关键词：

Serine protease; Irreversible inhibitor; Peptido sulfonyl fluoride; Electrophilic trap; Chymotrypsin; SOLID-PHASE SYNTHESIS; CANNABINOID CB1 RECEPTOR; PEPTIDOSULFONAMIDE; PEPTIDOMIMETICS; CYSTEINE; THREONINE; FOLDAMERS; TWEEZERS; AFFINITY; HYBRIDS;

D O I：

10.1016/j.bmc.2011.02.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have designed and synthesized novel irreversible serine protease inhibitors containing aliphatic sulfonyl fluorides as an electrophilic trap. These substituted taurine sulfonyl fluorides derived from taurine or protected amino acids were conveniently synthesized from beta-aminoethanesulfonyl chlorides using KF/18-crown-6 or from beta-aminoethanesulfonates using DAST. Their potency of irreversible inhibition of serine proteases is described in different enzyme assays using chymotrypsin leading to binding affinities up to 22 mu M. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2397 / 2406

页数：10

共 32 条

[1]

BARRETT AJ, 1986, RES MONOGRAPHS CELL, V12

[2] Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors [J].