Kakizawa Taeko, Hidaka Koushi, Hamada Daisuke, Yamaguchi Ryoji, Uemura Tsuyoshi, Kitamura Hitomi, Tagad Harichandra D, Hamada Takashi, Ziora Zyta, Hamada Yoshio, Kimura Tooru, Kiso Yoshiaki
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
J Pept Sci. 2010 Jun;16(6):257-62. doi: 10.1002/psc.1238.
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.
β-位点淀粉样前体蛋白裂解酶1（BACE1）已知参与阿尔茨海默病中β-淀粉样肽的产生，并且是当前药物设计的主要靶点。我们之前报道了基于底物的拟肽，即KMI化合物作为有效的BACE1抑制剂。在本研究中，我们设计并合成了作为低分子大小抑制剂的四肽。这些四肽对重组BACE1表现出高效力，其中KMI-927的IC（50）值最高，为34.6 nM。
