期刊
ACS CHEMICAL BIOLOGY
卷 15, 期 4, 页码 878-883出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.0c00090
关键词
-
资金
- Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [PTDC/BBB-BEP/2463/2014, SAICTPAC/0019/2015, UID/DTP/04138/2019, SFRH/BD/100400/2014, IF/00472/2014, IF/00656/2014]
- NIH [R01 DA033760]
- European Union [LISBOA-01-0145-FEDER-016405, 731005, LISBOA-01-0145-FEDER-007660, LISBOA-01-0145-FEDER-007344]
- FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) [LISBOA-01-0145-FEDER-007660]
- Fundacao para a Cie<^>ncia e a Tecnologia (FCT) [57/2017]
- FCT
- Fundação para a Ciência e a Tecnologia [PTDC/BBB-BEP/2463/2014, SFRH/BD/100400/2014] Funding Source: FCT
3-Oxo-beta-sultams are four-membered ring ambident clectrophiles that can react with nucleophiles either at the carbonyl carbon or at the sulfonyl sulfur atoms, and that have been reported to inhibit serine hydrolases via acylation of the active-site serine residue. We have developed a panel of 3-oxo-beta-sultam inhibitors and show, through crystallographic data, that they are regioselective sulfonylating electrophiles, covalently binding to the catalytic serine of human and porcine elastases through the sulfur atom. Application of 3-oxo-beta-sultam-derived activity-based probes in a human proteome revealed their potential to label disease-related serine hydrolases and proteasome subunits. Activity-based protein profiling applications of 3-oxo-beta-sultams should open up new opportunities to investigate these classes of enzymes in complex proteomes and expand the toolbox of available sulfur-based covalent protein modifiers in chemical biology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据