Zhong Jiaying, Gan Xiangdong, Alliston Kevin R, Groutas William C
Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
Bioorg Med Chem. 2004 Feb 1;12(3):589-93. doi: 10.1016/j.bmc.2003.10.059.
The design of novel functionalized templates capable of binding to the active site of serine proteases could potentially lead to the development of potent and highly selective non-covalent inhibitors of these enzymes. Using the elastase-turkey ovomucoid inhibitor complex and insights gained from earlier work based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I), a surrogate cyclosulfamide scaffold (II) was used for the first time in the design of reversible inhibitors of human leukocyte elastase. Compounds 7 and 8 were found to be micromolar reversible inhibitors of the enzyme.
设计能够与丝氨酸蛋白酶活性位点结合的新型功能化模板，可能会推动这些酶的强效且高选择性非共价抑制剂的开发。利用弹性蛋白酶 - 火鸡卵类粘蛋白抑制剂复合物以及基于1,2,5 - 噻二唑烷 - 3 - 酮1,1 - 二氧化物支架（I）的早期工作所获得的见解，首次将替代环磺酰胺支架（II）用于人白细胞弹性蛋白酶可逆抑制剂的设计。发现化合物7和8是该酶的微摩尔级可逆抑制剂。
