Author/Authors :
Baihua Hu، نويسنده , , Kristi Yi Fan، نويسنده , , Kristie Bridges، نويسنده , , Rajiv Chopra، نويسنده , , Frank Lovering، نويسنده , , Derek Cole، نويسنده , , Ping Zhou، نويسنده , , John Ellingboe، نويسنده , , Guixiang Jin، نويسنده , , Rebecca Cowling، نويسنده , , Jonathan Bard، نويسنده ,
Abstract :
A new series of bis-statine based peptidomimetic inhibitors of human β-secretase (BACE 1) was developed by structure-based modification of the three regions to the initial lead 3: an N-terminus, a central bis-statine core, and a C-terminus. Introduction of a 4-aminomethylbenzoic acid on the C-terminus resulted in a potent BACE 1 inhibitor with an IC50 value of 21 nM. The general requirements for the optimal substrate–enzyme interaction are disclosed herein.
