Inhibitors of beta-amyloid formation based on the beta-secretase cleavage site.
A series of inhibitors of beta-amyloid formation have been developed based on the beta-secretase cleavage site (VNL-DA) of the Swedish mutant Amyloid Precursor Protein. A simple tripeptide aldehyde was found to be the most potent (IC(50) = 700 nM) in the series displaying an inhibitory profile which is different from reported inhibitors of beta-amyloid formation.
Abbenante
G
G
Centre for Drug Design and Development, University of Queensland, Brisbane, Queensland, 4072, Australia.
Kovacs
D M
DM
Leung
D L
DL
Craik
D J
DJ
Tanzi
R E
RE
Fairlie
D P
DP
D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D015195:Drug Design; D010450:Endopeptidases; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013329:Structure-Activity Relationship
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human