Han 2025 — Dual perspectives on peptide–zinc complexation (aquatic and other natural origins)
Han, Dong, Yang, and Hu reviewed the chemistry, production, bioavailability, and clinical use of peptide–zinc complexes, with particular emphasis on zinc-chelating peptides derived from aquatic protein sources (oyster, sea cucumber, scallop, Alaska pollock, Antarctic krill, marine octopus, tilapia, pufferfish, silver carp). The framing is dietary supplementation of the essential trace element zinc through peptide carriers that improve solubility and intestinal absorption over inorganic salts such as ZnSO₄ and zinc gluconate. The review also touches on therapeutic chelation of free Zn²⁺ in Alzheimer’s disease (sequestration of Zn²⁺ to reduce Aβ₁–₄₀ aggregation). Zinc is not among the heavy metals tracked by HMI (Pb, tAs, Cd, MeHg, tHg, iAs, Ni, Al, Cr-VI, Sn); the source is recorded here for its mechanism content on peptide–metal coordination — binding groups (carboxylate, imidazole, sulfhydryl, amide carbonyl, phenolic hydroxyl), molecular-weight effects, hydrophobic-pocket encapsulation, and intestinal transport pathways — which is the same coordination chemistry that governs binding of toxic divalent metals such as Pb²⁺ and Cd²⁺ to food protein hydrolysates. No occurrence data for HMI-regulated heavy metals appear in this review.
Key numbers
The review compiles preparation conditions, peptide sequences, molecular weights, dissociation constants, and chelation rates from cited primary studies. Numbers below are copied as the review states them; none are HMI heavy metal occurrence values, and the dissociation constants and chelation rates concern Zn²⁺ binding to food-derived peptides, not toxic-metal binding to dietary matrices.
| Cited primary study | Source / peptide | Metal | Reported finding |
|---|---|---|---|
| Wang et al. (casein hydrolysate) [14] | TEDELQDKIHP (11-residue casein peptide) | Zn²⁺ | Chelate stability after simulated gastric digestion 78.54 ± 0.14% and after intestinal digestion 70.18 ± 0.17%. |
| Mukhamedov et al. (chickpea glutelin) [15] | HKERVQLHIIPTAVGK | Zn²⁺ | Chelating capacity 57.86 ± 2.14%; ICP-OS analysis 1 mg peptide chelates 381.61 ± 133.39 µg Zn; molar ratio peptide:Zn ≈ 1:4. |
| (review-stated, aquatic peptide context) | Seaweed peptides Asp residue proportion | Zn²⁺ | Aspartate residues 15–20% in seaweed peptides versus 5–8% in terrestrial plant peptides. |
| (review-stated, histidine pKa) | Histidine imidazole | Zn²⁺ | pKa ≈ 6.0; reported Kd range with Zn²⁺ 10⁻⁸–10⁻⁹ M. |
| (review-stated, Antarctic krill peptides) [11] | α-helical krill peptide | Zn²⁺ | Glu–His ligand spacing 0.3–0.5 nm (matches Zn²⁺ coordination radius); chelate half-life in simulated gastric fluid 8 h versus 2 h for random-coil peptides. |
| (review-stated, oyster peptide) [12] | -Asp-Glu- motif | Zn²⁺ | Binding rate 92%. |
| Sun et al. (scallop adductor hydrolysate) [4] | VDAALAK, DLGDIK, VTLEGK | Zn²⁺ | Three intestinal-transport peptides, each ≈ 600 Da, isolated from serosal side of rat intestinal sacs. |
| Chen et al. (oyster pepsin hydrolysate) [24] | HLRQEEKEEVTVGSLK | Zn²⁺ | Amino-nitrogen and carboxylate-oxygen identified by UV-vis and FTIR as main Zn²⁺ binding sites. |
| Liu et al. (sea cucumber body wall) [39] | WLTPTYPE (zinc-chelating peptide, ZCP) | Zn²⁺ | Representative ZCP sequence; molecular weight 1005.5 Da; endothermic Zn²⁺ binding with modest affinity (ITC); carboxylic-acid and amide groups identified as primary binding sites by FTIR. |
| Chen et al. (Alaska pollock skin) [38] | GPAGPHGPPG | Zn²⁺ | ≈ 75% (also reported as 74.8%) of GPAGPHGPPG remained intact after simulated GI digestion; zinc transport in Caco-2 cells enhanced 32.3% with concomitant retention reduced 60.2% and absorption reduced 13.8%. |
| Sun et al. (Antarctic krill, AKP-zinc) [4] | AKP–Zn chelate | Zn²⁺ | Preparation at pH 6.0, 60 °C, AKP:ZnSO₄·7H₂O mass ratio 1:2, reaction time 10 min; higher stability than ZnSO₄ or zinc gluconate under simulated GI digestion. |
| Jiang et al. (silver carp hydrolysate, flavor enzyme) [45] | EDLAKALAKK, GKKTAEIEK, QAVEAQK, KELEEK, YEESQAELEGSLK | Zn²⁺ | Five peptides selected for synthesis; native silver carp protein acidic-amino-acid content (Glu+Asp) ≈ 39%. |
| Zhang et al. (β-casein 1–25) [14] | β-casein 1–25 | Zn²⁺ | Zinc absorption rate in rabbits 30.03% versus 20.05% for ZnSO₄. |
| Liao et al. (walnut peptides, WP1) [70] | WP1–Zn complex | Zn²⁺ | Antiproliferative activity against human breast carcinoma cells via apoptosis induction; Zn–N and Zn–O covalent bonds reported by structural analysis. |
| (review-stated, oyster peptide affinity) [68 context] | oyster peptide | Zn²⁺ | Kd ≈ 5 × 10⁻⁷ M (within the 10⁻⁶–10⁻⁸ M range cited as physiologically effective for metal–peptide chelates). |
| Lakatos et al. (Alzheimer’s context) [65] | Histidine-rich branched peptides; salmon-skin His-X-His motif | Zn²⁺, Cu²⁺ | Aquatic-derived branched peptides bind two Zn²⁺ equivalents at physiological pH 7.4; inhibition of Zn²⁺-induced Aβ₁–₄₀ aggregation up to 58% in vitro. |
| (review-stated, intestinal paracellular pore) [83, 84] | Caco-2 tight-junction pore | — | Approximate pore size 2.1 nm. |
| (review-stated, zinc body content and tissue distribution) [13] | Human zinc distribution | Zn | Total body Zn 2–2.5 g; recommended adult daily intake ≤ 40 mg; approximate tissue Zn (µg/g wet weight): hair and nails 247, bone 100, liver 58, kidneys 55, muscle 51, pancreas 33.3, skin 32, heart 26.5, lung 16, intestine 15.5, spleen 14.7, stomach 13.4, brain 11, blood 8.06. |
The review states that aquatic peptides outperform terrestrial peptides for Zn²⁺ chelation primarily because their habitats (high salinity, high pressure, low temperature) selected for sequences enriched in aspartate, glutamate, and histidine, and for secondary-structure features (α-helices that fix Glu/His ligand spacing at the Zn²⁺ coordination radius; hydrophobic pockets formed by tertiary structure that exclude competing Ca²⁺ and Fe³⁺) that stabilize the chelate during gastrointestinal digestion. The dominant binding groups are imidazole (His), carboxylate from Asp and Glu side chains and C-terminus, sulfhydryl (Cys, prevalent in anaerobic-organism-derived peptides), phenolic hydroxyl (Tyr), and amide carbonyl. Reported transport pathways across intestinal epithelium include PepT1-mediated transport, paracellular permeation through tight junctions, transcytosis, and passive transcellular diffusion; peptide–zinc complexes are described as activating pathways not available to free peptides because the bound Zn²⁺ alters charge distribution and spatial structure.
Methods (brief)
This is a narrative review. The authors organize the field into ten sections: introduction (zinc biology and dietary forms), peptide–zinc chelation model and theoretical/coordination patterns, production and purification of zinc-chelating peptides from marine proteins (proteases, IMAC, RP-HPLC, MALDI-TOF and LC/MS/MS sequencing), zinc-chelating peptides of marine origin (oyster, scallop, Alaska pollock, Antarctic krill, octopus, sea cucumber, silver carp, tilapia), current insights into bioavailability (aquatic protein chelates, recent peptide–zinc interaction studies including molecular dynamics and FRET), clinical implications (nutritional supplements, Alzheimer’s-related Zn sequestration, noise-induced hearing loss, lack of direct clinical trial data with reference to iron and copper peptide chelation as proxy evidence), technological advances (ESI-MS, UV-vis, CD, fluorescence, QSAR modeling, hierarchical reaction logic for synthesis), intestinal zinc absorption (transcellular and paracellular pathways, Caco-2 studies), function and application (antioxidant, antibacterial, immunomodulatory, antiproliferative), and conclusions and future trends. The authors do not generate primary analytical data and do not measure or report contamination by Pb, Cd, As, Hg, Ni, Al, Cr-VI, Sn, Sb, or U in any food matrix.
Implications
The peptide–zinc coordination chemistry the review describes — coordination of divalent metal ions to imidazole nitrogen of histidine, carboxylate oxygen of aspartate and glutamate side chains and C-terminal carboxyl groups, sulfhydryl of cysteine, phenolic hydroxyl of tyrosine, and amide carbonyl oxygen — applies in principle to soft-acid divalent toxic metals (Pb²⁺, Cd²⁺, Hg²⁺) and to harder Lewis acids (e.g., Al³⁺, Cr³⁺) that coordinate to nitrogen-, oxygen-, and sulfur-donor ligands. The review is therefore useful background context for primary studies on whether food protein hydrolysates and casein phosphopeptide-containing matrices alter intestinal absorption or retention of dietary heavy-metal contaminants. The review itself reports no measurements on toxic-metal binding or bioavailability and should not be cited as evidence for any HMI standard, occurrence value, or bioaccessibility claim. The Alzheimer’s-disease section on histidine-rich aquatic peptides sequestering free Zn²⁺ to reduce Aβ aggregation is mechanistically relevant to literature on metal-mediated neurotoxicity but again does not contribute occurrence or dose data on HMI-regulated metals.
Verification notes
- PDF read in full (25 pages) via the Read tool; abstract, sections 1–10, Figures 1–6, and the full references list (94 entries) all reviewed.
- DOI
10.3390/biom15091311, raw handleMFK_49-dual-perspectives-on-peptide-zinc-complexation-, and cite-keyhan2025-peptide-zinc-complexation-aquatic-reviewchecked againstwiki/sources/; no existing page (DOI/handle/cite-key greps all empty). - Open access under CC-BY 4.0 per Wrexham University Research Online cover page and the MDPI Copyright notice on the first body page; recorded as
license: cc-by-4.0. - Metals discussed are Zn²⁺ (primary), with brief mentions of Cu²⁺ (Alzheimer’s branched peptides), Fe²⁺ (intestinal transport proxy for clinical-trial design discussion), Ca²⁺ (CPP zinc/calcium phytate nanocomplexes), and Aβ–Zn aggregation chemistry. None of HMI’s 10 HMTc analytes (Pb, tAs, Cd, MeHg, tHg, iAs, Ni, Al, Cr-VI, Sn) are measured or reviewed;
metals:is therefore[]. - The paper reports peptide sequences, molecular weights, chelation rates, and dissociation constants, not contamination occurrence values in food matrices;
ingredients:andproducts:are therefore[]. The aquatic protein sources cited (oyster, scallop, Alaska pollock skin, Antarctic krill, octopus, sea cucumber, tilapia, pufferfish, silver carp) are framed as carrier feedstocks for nutritional supplement manufacture and as protein-by-product valorization opportunities, not as products in which HMI heavy-metal contamination is being measured. Routing this source to ingredient or product pages would misrepresent the paper. matrices: [protein-hydrolysates, review-context]records what the paper actually concerns at the matrix level; this matches the convention used for adjacent peptide reviews lu2022-metal-chelating-peptides-review and irankunda2022-imac-mcp-separation-methodology-simulation in the same folder.jurisdictions: [GLOBAL]because the review compiles international primary literature; corresponding author at Dalian Minzu University (China) with a coauthor at Wrexham University (UK), but the literature surveyed is not jurisdiction-bound.- Brand firewall: no brand names appear in the review. Instrument vendors and column chemistries (IMAC, RP-HPLC, ESI-MS, MALDI-TOF, LC-Q-TOF) are method components, not brand attributions to contamination values.
- Wiki/HMTc firewall: no synthesis claims about contamination thresholds, occurrence values, or HMTc standards were imported from the review. The review does not bear on any HMI per-row P97/P45 calculation.
- Evidence tier: C (narrative review reporting findings from primary studies; no original data, no systematic-review methodology).
- Adjacent context: see wang2022-therapeutic-peptides-review, shalev2022-peptide-metal-nmr-review, luo2024-peptides-heavy-metal-remediation for related peptide-binding mechanism reviews already in the corpus.
Page history
The five most recent substantive edits to this page. The full version history lives in git; when DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.
| Commit | Date | Description |
|---|---|---|
| 1476f44 | 2026-06-09 | ingest: cacic2019-hemp-heavy-metals fresh from MFK/June 9 |