Ghosh A K, Bilcer G, Harwood C, Kawahama R, Shin D, Hussain K A, Hong L, Loy J A, Nguyen C, Koelsch G, Ermolieff J, Tang J
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA.
J Med Chem. 2001 Aug 30;44(18):2865-8. doi: 10.1021/jm0101803.
Memapsin 2 (beta-secretase) is one of two proteases that cleave the beta-amyloid precursor protein (APP) to produce the 40-42 residue amyloid-beta peptide (Abeta) in the human brain, a key event in the progression of Alzheimer's disease. On the basis of the X-ray crystal structure of our lead inhibitor (2, OM99-2 with eight residues) bound to memapsin, we have reduced the molecular weight and designed potent memapsin inhibitors. Structure-based design and preliminary structure-activity studies have been presented.
膜内天冬氨酸蛋白酶2（β-分泌酶）是两种蛋白酶之一，可切割β-淀粉样前体蛋白（APP），从而在人脑中产生40-42个残基的β-淀粉样肽（Aβ），这是阿尔茨海默病进展中的关键事件。基于我们与膜内天冬氨酸蛋白酶结合的先导抑制剂（2，含八个残基的OM99-2）的X射线晶体结构，我们降低了分子量并设计了强效的膜内天冬氨酸蛋白酶抑制剂。本文介绍了基于结构的设计和初步的构效关系研究。
