Collagen-derived Fe-chelating peptide: Key amino acids for Fe chelating and mechanisms for enhancing cellular Fe bioavailability.

This study aimed to identify the key amino acids and modes for chelation between peptides and Fe, characterize the structural and morphological differences, and explore the mechanisms by which peptide-Fe complexes enhanced cellular Fe bioavailability. The results demonstrated that the -Glu-Glu- motif played a crucial role in Fe chelation, adopting bidentate or multidentate chelating mode. Interestingly, although the C-terminal hydrophobic residues (Gly, Leu, Hyp, Pro) didn't directly chelate with Fe, they played an essential role in stabilizing the peptide conformation. Moreover, peptides and peptide-Fe complexes exhibited different structures and morphologies. Additionally, peptide-Fe complexes significantly enhanced cellular Fe transport/retention/utilization rate, increased intracellular ferritin levels, and modulated the expression of DMT1, PCBP2, and FPN1 proteins. The improvement of Fe transport by peptide-Fe complexes was mediated through multiple pathways including endocytosis, paracellular pathway, and DMT1. These findings can provide valuable insights for the development of Fe-chelating peptides as potential dietary iron supplements.