title: Tetrapeptides, as small-sized peptidic inhibitors; synthesis and their inhibitory activity against BACE1.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Kakizawa
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hamada
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uemura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Harichandra D
authors.initials: HD
authors.lastname: Tagad
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamada
authors.forename: Zyta
authors.initials: Z
authors.lastname: Ziora
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hamada
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: 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*
chemical_list: D016229:Amyloid beta-Peptides; D009842:Oligopeptides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human