Identification of zinc-binding peptides in ADAM17-inhibiting whey protein hydrolysates using IMAC-Zn2+ coupled with shotgun peptidomics

Abstract 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 < kDa) fractions, produced with Esperase (WPH-Esp), Everlase Savinase. Immobilized metal affinity chromatography (IMAC-Zn 2+ ) increased the capacity of peptide fraction (83%) when compared WPH-Esp (23%) its kDa (40%). The sample inhibitory activity against “a disintegrin metalloproteinase 17”. LC-MS/MS analysis using a shotgun peptidomics approach resulted in identification 24 originating bovine β-lactoglobulin, α-lactalbumin, serum albumin, β-casein, κ-casein, osteopontin-k, folate receptor-α fraction. identified contained different combinations strong group residues, His+Cys, Asp+Glu Phe+Tyr, although Cys residues absent sequences. silico predictions showed that IMAC-Zn non-toxins. However, possessed poor drug-like pharmacokinetic properties; was possibly due long chain lengths (5–19 residues). Taken together, work provided an array food peptide-based for further investigation structure-function relationships development nutraceuticals inflammatory other zinc-related diseases. Graphical abstract