Udechukwu, M. CDang, ChiUdenigwe, Chibuike C2021-02-022021-02-022021-02-02Food Production, Processing and Nutrition. 2021 Feb 02;3(1):5https://doi.org/10.1186/s43014-020-00048-4https://doi.org/10.20381/ruor-25958http://hdl.handle.net/10393/41736Abstract 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-Zn2+) 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 bovine β-lactoglobulin, α-lactalbumin, serum albumin, β-casein, κ-casein, osteopontin-k, and folate receptor-α in 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-Zn2+ 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. Graphical abstractJournal Article2021-02-02enThe Author(s)