Ovalbumin-derived peptides IFYCPIAIM, NIFYCPIAIM and YCPIAIMSA, containing a common region YCPIAIM, were previously identified as aggregation-prone peptides with variable fibril formation. In this study, we elucidated self-assembly mechanisms of the peptides, by determining the influence of self-assembly on sulfhydryl group accessibility. The free sulfhydryl group content and antioxidant capacity results demonstrate that the peptides assemble into β-sheets, possibly involving hydrogen bonding with the sulfhydryl groups. NIFYCPIAIM, IFYCPIAIM and YCPIAIMSA, in decreasing order, had the largest particle size, thioflavin T fluorescence, reactive sulfhydryl group content, and antioxidant activities. This demonstrates that the reactive sulfhydryl group content, which is influenced by the cysteine residue position relative to the N-terminal of the peptide, is dependent on fibrillation. Rheological studies further demonstrated the non-Newtonian shear-thinning behavior of the peptides. The results provide valuable insight on peptide self-assembly, which is imperative for future design of bioactive hydrogels with promising biomechanical properties for biomaterial applications.

Soluble epoxide hydrolase (sEH) contributes to the pathophysiology of neurodegenerative diseases by decreasing the epoxyeicosatrienoic acids/dihydroeicosatrienoic acids ratio and influencing the anti-inflammatory system. Thus, sEH inhibition reduces systemic inflammation, particularly in the brain. This study investigated sEH inhibition by a tetrapeptide, YMSV, and its mechanism of action. Enzyme inhibition kinetics demonstrated that YMSV is a mixed-competitive inhibitor of sEH, with a half-maximal inhibitory concentration (IC₅₀) of 179.5 ± 0.92 µM. Secondary structural analysis of sEH by circular dichroism showed that YMSV decreased the α-helices by 7.7% and increased the β-sheets and random coils by 11.4% and 22%, respectively. Molecular docking simulation indicated that YMSV formed a hydrogen bond with the Asp333 residue of the hydrolase pocket of sEH in addition to the binding of non-active site residues. The findings provide new insights into the mechanism of sEH inhibition by YMSV and its potential as a peptide-based anti-depressant nutraceutical.

Islet amyloid polypeptide (IAPP), or amylin, has been identified as a key factor in the development of type 2 diabetes (T2D). IAPP aggregates, which form amyloid fibrils, contribute to cytotoxicity of the pancreatic β-cells, resulting in loss of function and subsequent reduction in insulin production. As a result, surviving β-cells overcompensate for this reduction of insulin production, further contributing to the loss of function because of increased stress, thus leading to insulin resistance. Endogenously, IAPP monomers function in a variety of roles; however, aggregation renders them non-functional. The use of naturally occurring compounds, including peptides and phytochemicals, has been explored as a way to mitigate or inhibit IAPP fibril formation. This review discusses the structure, endogenous roles and mechanism of IAPP fibril formation, recent advances on inhibitors of IAPP fibril formation, and new insights on the future development and application of food-derived inhibitors towards T2D management.

Pyroglutamyl (pGlu) peptides are formed from intramolecular cyclization of glutamine or glutamic acid residue at the N-terminal position of peptides. This process can occur endogenously or during processing of foods containing the peptides. Some factors such as heat, high pressure and enzymatic modifications contribute to pGlu formation. pGlu peptides are thought to have different characteristics, especially bitter and umani tastes, and thus can affect the sensory properties of foods that contain them. Moreover, some health-promoting properties have been reported for pGlu peptides, including hepatoprotective, antidepressant and anti-inflammatory activities. However, the role of pGlu residue in the peptide bioactivity is not completely established, although the hydrophobic γ-lactam ring is thought to enhance the peptide stability against degradation by gastrointestinal proteases. This review discusses the occurrence and formation of pGlu peptides in foods, their quantification, sensory and biological properties, and prospects in food applications.

Peptides are important compounds used in the development of functional biomaterials, functional foods and nutraceuticals. The functional and bioactive properties of peptides are directly linked to their structural features, including molecular size, presence or absence of charges, amino acid sequence, hydrophobicity, and hydrophilicity. The role of peptide structures in their bioactivities and functionalities is still emerging. Some bioactive peptides have undesirable taste, which can influence consumer interests in novel peptide-based food applications. In this review, we discussed the role of peptide hydrophobicity in their bioavailability, bioactivity, bitterness property, emulsion stability, aggregation and self-assembly for application in novel food formulations and nutraceutical/drug delivery.