当前位置：
X-MOL 学术
›
ACS Chem. Biol.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
3-Oxo-β-sultam as a Sulfonylating Chemotype for Inhibition of Serine Hydrolases and Activity-Based Protein Profiling.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-03-20 , DOI: 10.1021/acschembio.0c00090 Luís A R Carvalho 1 , Vanessa T Almeida 2 , José A Brito 2 , Kenneth M Lum 3 , Tânia F Oliveira 2 , Rita C Guedes 1 , Lídia M Gonçalves 1 , Susana D Lucas 1 , Benjamin F Cravatt 3 , Margarida Archer 2 , Rui Moreira 1
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-03-20 , DOI: 10.1021/acschembio.0c00090 Luís A R Carvalho 1 , Vanessa T Almeida 2 , José A Brito 2 , Kenneth M Lum 3 , Tânia F Oliveira 2 , Rita C Guedes 1 , Lídia M Gonçalves 1 , Susana D Lucas 1 , Benjamin F Cravatt 3 , Margarida Archer 2 , Rui Moreira 1
Affiliation
|
3-Oxo-β-sultams are four-membered ring ambident electrophiles 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-β-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-β-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-β-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.
中文翻译：
3-Oxo-β-sultam作为抑制丝氨酸水解酶和基于活性的蛋白质谱分析的磺化化学型。
3-Oxo-β-sultams是可与羰基碳或磺酰基硫原子上的亲核试剂反应的四元环环境亲电试剂，并且据报道可通过将活性位丝氨酸残基酰化来抑制丝氨酸水解酶。我们已经开发了一组3-氧代-β-sultam抑制剂，并通过晶体学数据显示它们是区域选择性的磺酰化亲电试剂，通过硫原子共价结合到人和猪弹性蛋白酶的催化丝氨酸上。在人类蛋白质组中应用基于3-oxo-β-sultam的基于活性的探针显示了其潜在的标记疾病相关丝氨酸水解酶和蛋白酶体亚基的潜力。
更新日期：2020-04-23
中文翻译：
3-Oxo-β-sultam作为抑制丝氨酸水解酶和基于活性的蛋白质谱分析的磺化化学型。
3-Oxo-β-sultams是可与羰基碳或磺酰基硫原子上的亲核试剂反应的四元环环境亲电试剂，并且据报道可通过将活性位丝氨酸残基酰化来抑制丝氨酸水解酶。我们已经开发了一组3-氧代-β-sultam抑制剂，并通过晶体学数据显示它们是区域选择性的磺酰化亲电试剂，通过硫原子共价结合到人和猪弹性蛋白酶的催化丝氨酸上。在人类蛋白质组中应用基于3-oxo-β-sultam的基于活性的探针显示了其潜在的标记疾病相关丝氨酸水解酶和蛋白酶体亚基的潜力。
京公网安备 11010802027423号