Yang Qingliang, Li Yi, Dou Dengfeng, Gan Xiangdong, Mohan Swathi, Groutas Christopher S, Stevenson Laura E, Lai Zhong, Alliston Kevin R, Zhong Jiaying, Williams Todd D, Groutas William C
Department of Chemistry, Wichita State University, 1845 N Fairmount Avenue, Wichita, KS 67260, USA.
Arch Biochem Biophys. 2008 Jul 15;475(2):115-20. doi: 10.1016/j.abb.2008.04.020. Epub 2008 Apr 22.
A new class of carbamylating agents based on the cyclosulfamide scaffold is reported. These compounds were found to be efficient time-dependent inhibitors of human neutrophil elastase (HNE). Exploitation of the three sites of diversity present in the cyclosulfamide scaffold yielded compounds which inhibited HNE but not proteinase 3 (PR 3) or bovine trypsin. The findings reported herein suggest that the introduction of appropriate recognition elements into the cyclosulfamide scaffold may lead to highly selective agents of potential value in the design of activity-based probes suitable for investigating proteases associated with the pathogenesis of chronic obstructive pulmonary disease.
报道了一类基于环硫酰胺骨架的新型氨甲酰化剂。这些化合物被发现是人类中性粒细胞弹性蛋白酶（HNE）的有效时间依赖性抑制剂。对环硫酰胺骨架中存在的三个多样性位点进行开发，得到了抑制HNE但不抑制蛋白酶3（PR 3）或牛胰蛋白酶的化合物。本文报道的研究结果表明，在环硫酰胺骨架中引入适当的识别元件可能会产生具有潜在价值的高选择性试剂，用于设计基于活性的探针，以研究与慢性阻塞性肺疾病发病机制相关的蛋白酶。
