Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases

Y Liu, W Zhang, L Li, LA Salvador, T Chen…

Index: Liu, Yanxia; Zhang, Wei; Li, Li; Salvador, Lilibeth A.; Chen, Tiantian; Chen, Wuyan; Felsenstein, Kevin M.; Ladd, Thomas B.; Price, Ashleigh R.; Golde, Todd E.; He, Jianhua; Xu, Yechun; Li, Yingxia; Luesch, Hendrik Journal of Medicinal Chemistry, 2012 , vol. 55, # 23 p. 10749 - 10765

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Citation Number: 14

Abstract

Inspired by marine cyanobacterial natural products, we synthesized modified peptides with a central statine-core unit, characteristic for aspartic protease inhibition. A series of tasiamide B analogues inhibited BACE1, a therapeutic target in Alzheimer's disease. We probed the stereospecificity of target engagement and determined additional structure–activity relationships with respect to BACE1 and related aspartic proteases, cathepsins D and E. ...