ABSTRACT
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 cleaved in silico by gastrointestinal proteases, and the 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. A novel anti-AD tripeptide WIR with potent inhibition of AChE and BACE 1 was identified, with IC50 values of 43.32 ± 1.22 µM and 2.27 ± 0.35 mM, respectively. In addition, the inhibition rate of WIR (at a concentration of 1.06 ± 0.87 µM) against BChE was 33.5%, and the peptide WIR was able to simultaneously interact with AChE, BChE, and BACE 1. Residues Ser286 of AChE, Asp70 of BChE, and Thr231, Arg235 of BACE 1 played key roles in the interaction with peptide WIR. In summary, peptide WIR exhibits the potential to be an effective treatment for AD.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Aspartic Acid Endopeptidases/antagonists & inhibitors , Cholinesterase Inhibitors/pharmacology , Fishes , Molecular Docking Simulation , Ovum/chemistry , Peptides/pharmacology , Acetylcholinesterase , Alzheimer Disease/drug therapy , Animals , Butyrylcholinesterase , Catalytic Domain , Cholinesterase Inhibitors/chemistry , Humans , Hydrogen Bonding , Models, Molecular , Peptides/chemistry , SolubilityABSTRACT
BACKGROUND: Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease that affects the elderly. There is no ideal treatment for AD. Thus, the purpose of this study is to identify anti-AD peptides from ovalbumin. RESULTS: The potential tripeptides IEK, LYR, and CIK were selected for molecular docking. The '-CDOCKER_Energy' values of the best docking positions of the tripeptide IEK, LYR, and CIK interacting with acetylcholinesterase (AChE) were 93.8119, 86.9556 and 73.6370 kcal mol-1 , respectively. The '-CDOCKER_Energy' values for interaction with butyrylcholinesterase (BChE) were 96.6386, 80.8392, and 87.4341 kcal mol-1 , respectively. Most importantly, the '-CDOCKER_Energy' values for interaction with ß-site amyloid precursor protein cleavage enzyme1 (BACE1) were 85.5903, 71.3342, and 68.4290 kcal mol-1 , respectively. Overall, in vitro assay results demonstrated that the peptide CIK exhibited impressive inhibitory activities against AChE, BChE, and BACE1, with half maximal inhibitory concentration (IC50 ) values of 6.76, 7.72, and 34.48 µmol L-1 , respectively. In particular, CIK can be joined with some peripheral anion sites (PAS) and catalytic sites on AChE, BChE, and BACE1. CONCLUSION: Tripeptide CIK can effectively inhibit the activities of AChE, BChE, and BACE1. Tripeptide CIK therefore has the potential to treat AD effectively. © 2020 Society of Chemical Industry.
