Identification and molecular docking study of fish roe-derived peptidesas potent BACE 1, AChE and BChE inhibitors
Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1(BACE 1) play vital roles in the development and progression of Alzheimer’s disease (AD). The objective of the present study was to identify fish roe-derived anti-AD peptides with activities against AChE, BChE, and BACE 1. Fish roe proteins were in silico cleaved by gastrointestinal proteases, and released peptides were collected. Subsequently, the toxicity, solubility, and biological properties of these novel di- and tri-peptides were predicted and validated. Finally, potential anti-AD peptides were docked to targets, i.e., AChE, BChE, and BACE 1. As a result, a novel anti-AD tripeptide WIR with potent AChE and BACE 1 inhibitory activity was identified, with IC50 value of 43.32±1.22 μM and 2.27±0.35 mM, respectively. In addition, the inhibition rate of WIR (at the concentration of 1.06±0.87 µM) against BChE was 33.5%. And the peptide WIR was able to interact with AChE, BChE and BACE 1simultaneously. Especially, residues Ser286 of AChE, Asp70 of BChE, and Thr231, Arg235 of BACE 1 played key role in the interaction of peptide WIR. In summary, peptide WIR has the potential to be a candidate for the treatment of AD.