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.
MeSH terms
-
Amyloid Precursor Protein Secretases
-
Aspartic Acid Endopeptidases / antagonists & inhibitors*
-
Brain / enzymology
-
Endopeptidases
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / chemistry
-
Humans
-
Models, Molecular
-
Oligopeptides / chemical synthesis*
-
Oligopeptides / chemistry
-
Structure-Activity Relationship
-
Substrate Specificity
Substances
-
Enzyme Inhibitors
-
Oligopeptides
-
Amyloid Precursor Protein Secretases
-
Endopeptidases
-
Aspartic Acid Endopeptidases
-
BACE2 protein, human
-
BACE1 protein, human