Tetrapeptides, as small-sized peptidic inhibitors; synthesis and their inhibitory activity against BACE1

✍ Scribed by Taeko Kakizawa; Koushi Hidaka; Daisuke Hamada; Ryoji Yamaguchi; Tsuyoshi Uemura; Hitomi Kitamura; Harichandra D. Tagad; Takashi Hamada; Zyta Ziora; Yoshio Hamada; Tooru Kimura; Prof. Yoshiaki Kiso

• Book ID: 105359868
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 196 KB
• Volume: 16
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1238

✦ Synopsis

Abstract

β‐Site amyloid precursor protein cleaving enzyme 1 (BACE1) is known to be involved in the production of amyloid β‐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. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.