Peptide–Mineral Complexes: Understanding Their Chemical Interactions, Bioavailability, and Potential Application in Mitigating Micronutrient Deficiency

Abstract

Iron, zinc, and calcium are essential micronutrients that play vital biological roles to maintain human health. Thus, their deficiencies are a public health concern worldwide. Mitigation of these deficiencies involves micronutrient fortification of staple foods, a strategy that can alter the physical and sensory properties of foods. Peptide–mineral complexes have been identified as promising alternatives for mineral-fortified functional foods or mineral supplements. This review outlines some of the methods used in the determination of the mineral chelating activities of food protein-derived peptides and the approaches for the preparation, purification and identification of mineral-binding peptides. The structure–activity relationship of mineral-binding peptides and the potential use of peptide–mineral complexes as functional food ingredients to mitigate micronutrient deficiency are discussed in relation to their chemical interactions, solubility, gastrointestinal digestion, absorption, and bioavailability. Finally, insights on the current challenges and future research directions in this area are provided.

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

“…The whey protein hydrolysates were evaluated for zinc binding as previously reported (Jakob et al 2000). The assay principle is based on the reaction of 4-(2-pyridylazo) resorcinol with free zinc ions in solution to form a red coordination complex (Sun et al 2020). The peptide samples and reagents were prepared in 40 mM HEPES-KOH buffer (pH 7.5).…”

“…This demonstrates an efficient separation of the zinc-binding peptides. Peptides separate on IMAC columns based on their interaction with immobilized metal ions (Sun et al 2020). Peptidic metal ligands, such as Asp, Glu and His, are deprotonated at neutral-basic pH conditions and hence form reversible metal complexes on the IMAC-Zn 2+ column (Block et al 2009), which dissociate at acidic pH (Cheung, Wong, and Ng 2012).…”

“…Food proteins are rich sources of peptides with an inherent capacity to bind divalent metals, such as zinc (Sun et al 2020). Zinc is a Lewis acid and can serve as an electron pair acceptor from Lewis bases, such as amino acid ligands.…”

“…Zinc is a Lewis acid and can serve as an electron pair acceptor from Lewis bases, such as amino acid ligands. Thus, the zinc-binding property of food peptides is due to their structural composition of specific amino acid residues, such as His, Cys, Asp, Glu, Phe and Tyr, whose functional side chains act as nucleophilic ligands to form coordinate complexes with zinc (Bischoff and Schlüter 2012; Udechukwu et al 2016;Walters et al 2018;Sun et al 2020). Such zinc-binding peptides could have useful nutritional applications as dietary zinc carriers to enhance zinc bioaccessibility and bioavailability (Walters et al 2018;Udechukwu et al 2016Udechukwu et al , 2018.…”

“…Zinc-binding peptides are usually produced from food proteins following bioassay-guided procedures, which typically begin with enzymatic hydrolysis and release of the peptide ligands from the parent proteins. The protein hydrolysates are then subjected to post-hydrolysis processing/ purification steps, involving immobilized metal (Zn 2+ ) affinity chromatography (IMAC-Zn 2+ ), in which peptides with high affinity for zinc are retained on the chromatographic column and retrieved during the elution step (Sun et al 2020). Using IMAC, some studies derived zinc-binding peptides, including LAN, SM and NCS from sesame proteins (Wang et al 2012); AR, GKR, EPSH and NSM from rapeseed proteins (Xie et al 2015); a 16-mer peptide from oyster proteins (Chen et al 2013); and 10-mer and 12-mer peptides from wheat germ proteins (Zhu et al 2015).…”