Tetrapeptides, as small-sized peptidic inhibitors; synthesis and their inhibitory activity against BACE1.
Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is known to be involved in the production of amyloid beta-peptide in Alzheimer's disease and is a major target for current drug design. We previously reported substrate-based peptidomimetics, KMI-compounds as potent BACE1 inhibitors. In this study, we designed and synthesized tetrapeptides as low molecular-sized inhibitors. These exhibited high potency against recombinant BACE1, with the highest IC(50) value of 34.6 nM from KMI-927.
Kakizawa
Taeko
T
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
Hidaka
Koushi
K
Hamada
Daisuke
D
Yamaguchi
Ryoji
R
Uemura
Tsuyoshi
T
Kitamura
Hitomi
H
Tagad
Harichandra D
HD
Hamada
Takashi
T
Ziora
Zyta
Z
Hamada
Yoshio
Y
Kimura
Tooru
T
Kiso
Yoshiaki
Y
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D009842:Oligopeptides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human