Aspartic protease (AP) plays an essential role in serious diseases, and thus, is thought to be a suitable target to design therapeutic inhibitors. In the present study, we focused on Beta-site Amyloid precursor protein Cleaving Enzyme-1 (BACE1), an aspartic protease involved in the production of amyloid β peptide (Aβ) in Alzheimer's disease.
The hydroxyethylamine scaffold was constructed from Z-Leu-OH using a Mannich-type reaction as a key reaction. Completion of the synthesis of hydroxyethylamine derivatives was accomplished by the coupling reaction of the hydroxyethylamine scaffold and a peptide sequence followed by deprotection and HPLC-purification. The inhibitory activity of the synthesized compound was evaluated using a recombinant BACE1 (rBACE1).
