Identification of zinc-binding peptides in ADAM17-inhibiting whey protein hydrolysates using IMAC-Zn^(2+) coupled with shotgun peptidomics  

作　　者：M.Chinonye Udechukwu Chi Dang Chibuike C.Udenigwe 

机构地区：[1]Department of Plant,Food,and Environmental Sciences,Faculty of Agriculture,Dalhousie University,Truro,Nova Scotia B2N 5E3,Canada [2]Department of Chemistry and Biomolecular Sciences,Faculty of Science,University of Ottawa,Ottawa,Ontario K1N 6N5,Canada [3]School of Nutrition Sciences,Faculty of Health Sciences,University of Ottawa,Ottawa,Ontario K1H 8M5,Canada

出　　处：《Food Production, Processing and Nutrition》2021年第1期70-79,共10页食物生产加工与营养（英文）

基　　金：supported by the Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grants(RGPIN-435865-2013 and RGPIN-2018-06839);Canada Foundation for Innovation(CFI)John R.Evans Leaders Fund Infrastructure Grant(Project number:31305).

摘　　要：Food components possessing zinc ligands can be used to inhibit zinc-dependent enzymes.In this study,zinc-binding peptides were derived from whey protein hydrolysates,and their ultrafiltration(>1 and<1 kDa)fractions,produced with Esperase(WPH-Esp),Everlase and Savinase.Immobilized metal affinity chromatography(IMAC-Zn^(2+))increased the zinc-binding capacity of the peptide fraction(83%)when compared to WPH-Esp(23%)and its<1 kDa fraction(40%).The increased zinc-binding capacity of the sample increased the inhibitory activity against the zinc-dependent“a disintegrin and metalloproteinase 17”.LC-MS/MS analysis using a shotgun peptidomics approach resulted in the identification of 24 peptides originating from bovineβ-lactoglobulin,α-lactalbumin,serum albumin,β-casein,κ-casein,osteopontin-k,and folate receptor-αin the fraction.The identified peptides contained different combinations of the strong zinc-binding group of residues,His+Cys,Asp+Glu and Phe+Tyr,although Cys residues were absent in the sequences.In silico predictions showed that the IMAC-Zn^(2+)peptides were non-toxins.However,the peptides possessed poor drug-like and pharmacokinetic properties;this was possibly due to their long chain lengths(5–19 residues).Taken together,this work provided an array of food peptide-based zinc ligands for further investigation of structure-function relationships and development of nutraceuticals against inflammatory and other zinc-related diseases.

关 键 词：ZINC Zinc ligands Food protein Bioactive peptides Immobilized metal affinity chromatography Ultrafiltration ADAM17 PEPTIDOMICS Bioinformatics 

分 类 号：O62[理学—有机化学]