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

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 IC50 value of 34.6 nM from KMI‐927. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. Tetrapeptidic BACE1 inhibitors were designed and synthesized. Inhibitory activity was determined by in vitro enzymatic assay. Our tetrapeptides exhibited high potency, with the highest IC50 value of 34.6 nM from KMI‐927.