n -芳基磺酰基琥珀酰亚胺活性探针的合成及评价。

IF 1.4 4区 化学 Q3 CHEMISTRY, ORGANIC
Synlett Pub Date : 2025-10-01 Epub Date: 2025-05-25 DOI:10.1055/s-0043-1775487
Jo Chvatal, Dat T Nguyen, Alexondra S Xie, William H Parsons
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引用次数: 0

摘要

基于活性的蛋白质谱分析(ABPP)技术作为研究蛋白质的一个强大平台已有二十多年的历史。然而,这一领域的进一步发展取决于新的探针结构的发展,以扩大使用这些方法可以研究的蛋白质组的比例。受先前报道的含有琥珀酰亚胺的共价蛋白酶抑制剂的启发,我们合成了一组具有琥珀酰亚胺反应基团和末端炔标签的潜在探针结构,适用于随后的叠氮-炔点击化学。该小组的成员与n -芳基磺酰基连接产生纯化丝氨酸蛋白酶和蛋白质在复杂的细胞裂解物的标记。我们发现其中一种探针在低微摩尔浓度下标记人菱形蛋白酶RHBDL2,并且可以与活性位点抑制剂竞争。我们的研究为开发基于活性的探针提供了一个新的反应基团,并为研究一类功能表征有限的酶提供了一个新的化学工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and evaluation of N-arylsulfonylated succinimides as activity-based probes.

Activity-based protein profiling (ABPP) technology has served as a powerful platform for studying proteins for more than two decades. However, the further growth of this field depends on the development of new probe structures to expand the proportion of the proteome that can be studied using these methods. Inspired by previous reports of succinimide-containing covalent inhibitors for proteases, we synthesized a panel of potential probe structures with a succinimide reactive group and a terminal alkyne tag suitable for subsequent azide-alkyne click chemistry. Members of this panel with an N-arylsulfonyl linker produce labeling of both purified serine proteases as well as proteins in complex cellular lysates. We found that one of these probes labels the human rhomboid protease RHBDL2 at low micromolar concentrations and can be competed with active-site inhibitors. Our studies establish succinimide as a new reactive group for the development of activity-based probes and offer a new chemical tool for studying a class of enzymes with limited functional characterization.

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来源期刊
Synlett
Synlett 化学-有机化学
CiteScore
3.40
自引率
5.00%
发文量
369
审稿时长
1 months
期刊介绍: SYNLETT is an international journal reporting research results and current trends in chemical synthesis in short personalized reviews and preliminary communications. It covers all fields of scientific endeavor that involve organic synthesis, including catalysis, organometallic, medicinal, biological, and photochemistry, but also related disciplines and offers the possibility to publish scientific primary data.
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