Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin  

作　　者：Zhipeng Yu Sijia Wu Wenzhu Zhao Long Ding David Shiuan Fuping Zheng Jianrong Li Jingbo Liu 

机构地区：[1]College of Food Science and Engineering,National&Local Joint Engineering Research Center of Storage,Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products,Bohai University,Jinzhou,121013,PR China [2]Beijing Advanced Innovation Center for Food Nutrition and Human Health,Beijing Technology and Business University(BTBU),Beijing,102488,PR China [3]College of Food Science and Engineering,Northwest A&F University,Yangling,712100,PR China [4]Lab of Nutrition and Functional Food,Jilin University,Changchun,130062,PR China

出　　处：《Food Science and Human Wellness》2020年第2期162-167,共6页食品科学与人类健康（英文）

基　　金：This work was supported by the National Natural Science Funds of China(No.31901635);the National Key Research and Development Program of China(2018YFD0400301).

摘　　要：Inhibition of beta-site APP cleaving enzyme1(BACE1)is one of the most promising therapeutic approaches for Alzheimer’s disease.To find natural products for the treatment of Alzheimer’s disease,absorption,distribution,metabolism,excretion and toxicity(ADMET)properties and in vitro BACE1 inhibitory activity of the peptides isolated from egg albumin were evaluated.Then,molecular docking and molecular dynamics simulation were used to explain the molecular mechanism of the interactions between BACE1 and peptides.The IC50 value of peptide KLPGF,with satisfactory ADMET properties,against BACE1 was(8.30±0.56)mmol/L.Molecular docking revealed that KLPGF contacted with the residues of BACE1’s active sites through twelve hydrogen bonds interactions,two hydrophobic interactions,one electrostatic interaction,and two Pi-cation interactions.The 5 ns molecular dynamics simulations confirmed that the structure of KLPGF with BACE1 was stable.Peptide KLPGF contacted the residues Lys321,Asp228,and Asn233 with stable hydrogen bonds.KLPGF may be a potential anti-BACE1 candidate.

关 键 词：Alzheimer’s disease BACE1 ADMET prediction Molecular docking Molecular dynamics KLPGF 

分 类 号：TQ464.7[化学工程—制药化工]