2. Academic Validation
  3. Design of substrate-based inhibitors of human beta-secretase

Design of substrate-based inhibitors of human beta-secretase

  • J Med Chem. 2002 Jan 17;45(2):259-62. doi: 10.1021/jm0155695.
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
PMID: 11784130 DOI: 10.1021/jm0155695
Abstract

By use of the effectively cleaved Beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) 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.

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