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: Taeko Kakizawa, Koushi Hidaka, Daisuke Hamada, Ryoji Yamaguchi, Tsuyoshi Uemura, Hitomi Kitamura, Harichandra D Tagad, Takashi Hamada, Zyta Ziora, Yoshio Hamada, Tooru Kimura, Yoshiaki Kiso
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) Vol. 16 Issue 6 Pg. 257-62 (Jun 2010) ISSN: 1099-1387 [Electronic] England
• PMID: 20474036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 European Peptide Society and John Wiley & Sons, Ltd.

Chemical References

• Amyloid beta-Peptides
• Oligopeptides
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• BACE1 protein, human

Topics

• Amyloid Precursor Protein Secretases (antagonists & inhibitors)
• Amyloid beta-Peptides (metabolism)
• Aspartic Acid Endopeptidases (antagonists & inhibitors)
• Drug Design
• Drug Evaluation, Preclinical
• Inhibitory Concentration 50
• Molecular Structure
• Oligopeptides (chemistry, genetics, metabolism)