jm0155695_si_001.pdf (44.15 kB)
Design of Substrate-Based Inhibitors of Human β-Secretase
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 JohnBy 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.