Author/Authors :
Jingdan Hu، نويسنده , , Cynthia L. Cwi، نويسنده , , David L. Smiley، نويسنده , , David Timm، نويسنده , , Jon A. Erickson، نويسنده , , James E. McGee، نويسنده , , Hsiu-Chiung Yang، نويسنده , , David Mendel، نويسنده , , Patrick C. May، نويسنده , , Mike Shapiro، نويسنده , , James R. McCarthy، نويسنده ,
Abstract :
Utilizing structure-based techniques and solid-phase synthesis, statine-based tetrapeptide BACE inhibitors were designed and synthesized using a heptapeptide BACE transition-state mimetic, 1, as the starting point. Structure–activity relationship studies at the P3, P2, and P2′ positions as well as the N-terminal capping group on scaffold 5 led to the discovery of potent inhibitors 27, 32, and 34 (IC50<100 nM). In addition, computational analysis and the X-ray structure of BACE–inhibitor 38 are discussed.
