Marine organisms have evolved a remarkable arsenal of host-defense peptides under conditions of extreme variability and constant pathogen exposure. Generally defined as short chains of 2 to 20 amino acid residues, these molecules have become a focal point for biomedicine, food science, and materials science. In a review published in the Chinese Journal of Natural Medicines , researchers from the School of Pharmacy at China Pharmaceutical University provide an integrated overview of how marine bioactive peptides are produced, purified, and evaluated, and how bioinformatics is reshaping the discovery pipeline.
Peptide production has expanded well beyond classical solvent extraction and chemical hydrolysis. Green deep eutectic solvents have recovered collagen peptides from cod skin with extraction efficiencies of 96%, while enzymatic hydrolysis and microbial fermentation enable targeted release of bioactive sequences. For example, fermentation of scallop skirt with a high-altitude Bacillus strain yielded the iron-chelating heptapeptide FEDPEFE while cutting production cost by up to 50%. Once released, peptides are resolved by membrane separation, multi-mode chromatography, and capillary electrophoresis, with nano-reversed-phase ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry now enabling accurate sequencing of trace peptides from complex hydrolysates.
The review surveys six major activity categories. Anti-inflammatory peptides such as the phycocyanin-derived PCP3 act through the Akt and AMPK/autophagy pathways, while the Sipunculus nudus tripeptide SRP attenuates cadmium-induced kidney injury via MAPK signaling. Antimicrobial peptides from Antarctic icefish and other species disrupt bacterial membranes and bind microbial DNA, offering candidates against multidrug-resistant pathogens. Antioxidant peptides scavenge free radicals and modulate Keap1/Nrf2 signaling. Anticancer peptides such as MP06 from green algae induce apoptosis in non-small cell lung cancer cells. Antihypertensive peptides like LEPWR and TLRFALHGME inhibit angiotensin-converting enzyme with low-micromolar potency, and antidiabetic peptides improve glycemic control through DPP-IV inhibition and the PI3K/AKT and AMPK pathways.
A central theme is the rise of bioinformatics. Virtual proteolysis using BIOPEP, PeptideCutter, and EnzymePredictor lets researchers triage candidate sequences before laboratory work. Structural prediction platforms such as AlphaFold2, ESMFold, and RoseTTAFold now generate high-confidence three-dimensional models for structure-guided design, and the authors flag the newer AlphaFold3 as a particularly promising tool. Quantitative structure-activity relationship modeling, residue-pattern analysis, and molecular docking, validated by cellular thermal shift assays and surface plasmon resonance, complete the computational layer that links sequence to function.
On the translational side, the global marine peptide market was valued at approximately USD 310 million in 2023, with a projected compound annual growth rate of 6.7%. Yet only a small number of marine peptide drugs, such as ziconotide for severe chronic pain and plitidepsin for multiple myeloma, have reached approval, with several promising candidates discontinued because of toxicity or unfavorable pharmacokinetics. The authors argue that strategies such as cyclization, D-amino acid substitution, PEGylation, conjugation with cell-penetrating peptides, and AI-driven optimization of ADME properties, together with multi-omics analysis and intelligent delivery systems, can move marine peptides from laboratory leads to next-generation drugs, functional foods, and nutraceuticals.
Original article: https://doi.org/10.1016/S1875-5364(26)61178-8
Chinese Journal of Natural Medicines
Literature review
Not applicable
Marine-derived products as pharmaceutical treasure troves: a focus on recent research techniques and potential bioactive activities of marine peptides
11-May-2026