Food-derived zinc- and ferrous-chelating peptides and peptide-zinc/ferrous complexes: AI-assisted screening, bioavailability mechanisms, and bioactivities.
TL;DR
Reports of low-molecular-weight peptides are mainly low-molecular-weight peptides, but their activity is better explained by local coordination microenvironments than by MW or net charge alone.
Abstract
Background
Zinc and iron deficiencies remain widespread, while conventional inorganic fortificants are limited by poor solubility, susceptibility to dietary antagonists, and regulated epithelial uptake. Food-derived metal-chelating peptides (MCPs), particularly zinc-chelating peptides (ZCPs) and ferrous-chelating peptides (FCPs), can coordinate Zn2+ or Fe2+, improve mineral stability and availability, and may provide additional sequence-dependent bioactivities. However, their structure-function rules, intestinal absorption forms, and AI-assisted discovery strategies remain insufficiently defined. Scope and approach: This review summarizes the preparation, purification, identification, and structure-function relationships of food-derived ZCPs and FCPs. It further evaluates the current role of bioinformatics and artificial intelligence in MCP discovery, compares the intact complex absorption and competitive absorption hypotheses, and discusses evidence from in vitro and in vivo studies on the bioavailability and biological activities of peptide-Zn complexes, peptide-Fe complexes, and broader peptide-metal complexes. KEY
Findings
AND
Conclusions
Reported ZCPs and FCPs are mainly low-molecular-weight peptides, but their activity is better explained by local coordination microenvironments than by MW or net charge alone. Key determinants include donor-atom density, acidic or phosphorylated clusters, terminal groups, residue arrangement, and coordination geometry. AI-assisted screening can help prioritize candidate MCPs, but reliable prediction is constrained by heterogeneous peptide-metal datasets. Current evidence supports peptide-assisted Zn2+/Fe2+ absorption and source-dependent bioactivities, although the absorbed metal species remains insufficiently defined. Future studies should combine standardized datasets, chemical speciation, and isotope- or dual-label-based validation to support practical application of peptide-metal complexes.
