American Chemical Society
Browse
jm0155695_si_001.pdf (44.15 kB)

Design of Substrate-Based Inhibitors of Human β-Secretase

Download (44.15 kB)
journal contribution
posted on 2001-12-20, 00:00 authored by Jay S. Tung, David L. Davis, John P. Anderson, Don E. Walker, Shumeye Mamo, Nancy Jewett, Roy K. Hom, Sukanto Sinha, Eugene D. Thorsett, Varghese John
By use of the effectively cleaved β-secretase (BACE) substrate (1), incorporation of a statine in P1 resulted in a weak inhibitor 13 of the enzyme. Further substitution of P1‘-Asp by P1‘-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P10−P5 residues on the N-terminal part of inhibitor 22 resulted in no loss of potency (23). C-terminal truncations of inhibitor 22 generally led to significant loss of potency.

History