title: Design of substrate-based inhibitors of human beta-secretase.
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.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Tung
authors.forename: David L
authors.initials: DL
authors.lastname: Davis
authors.forename: John P
authors.initials: JP
authors.lastname: Anderson
authors.forename: Don E
authors.initials: DE
authors.lastname: Walker
authors.forename: Shumeye
authors.initials: S
authors.lastname: Mamo
authors.forename: Nancy
authors.initials: N
authors.lastname: Jewett
authors.forename: Roy K
authors.initials: RK
authors.lastname: Hom
authors.forename: Sukanto
authors.initials: S
authors.lastname: Sinha
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Thorsett
authors.forename: Varghese
authors.initials: V
authors.lastname: John
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001921:Brain / Q000201:enzymology; D010450:Endopeptidases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human