INFORM June 2026

26 INFORM JUNE 2026 , VOL. 37, NO. 6

For example, short peptides like soy have been shown to exhibit ACE inhibitor activity, whereas chickpea peptide has been reported to have anticancer effects. In addition, numerous plant peptides possess high antioxidant capacity. When amino acids are incorporated into peptide chains, their antioxidant effects can become additive or synergistic, leading to enhanced activity compared to individual amino acids. This means that not just the presence, but the sequence and structural arrangement of amino acids ultimately determine the function of antioxidant peptides. Smaller peptides, especially those below ~3 kDa, consistently show higher radical scavenging and lipid peroxidation inhibition compared to larger ones. In terms of residues, amino acids like tryptophan, tyrosine, histidine, methionine, and lysine are associated with stronger antioxidant activity. Peptides containing tryptophan and histidine tend to perform better because tryptophan can donate hydrogen easily, while the imidazole ring of histidine helps in radical trapping and metal chelation. Sequence also matters. Small changes in residue order affect antioxidative function. A good example is the peptide ISELGW, a strong inhibitor of lipid peroxidation. Researchers determined that replacing

some residues maintained activity, while others significantly reduced activity. There are also clear effects of specific residue combinations. Peptides that combine hydrophobic residues with aromatic residues show stronger interaction with lipid radicals, inhibiting oxidation. Repeating units also seems to play a role. Peptides containing repeats show improved activity, likely due to synergistic effects. Hydrophobic repeats improve interaction with lipid systems, while others enhance electron donation and metal ion interactions. Structural features further influence activity. Having hydrophobic residues at the N-terminus improves peptide partitioning into lipid phases, increasing proximity to reactive radicals. DISCOVERING BIOACTIVE PEPTIDES The production of peptides generally follows two main approaches. One involves enzymatic hydrolysis or microbial fermentation to break proteins down into smaller peptide fragments, resulting in a complex mixture of different bioactive peptides (top-down process). The other approach is bottom-up synthesis, in which peptides are assembled from individual amino acids using chemical methods (solid-phase peptide synthesis). This approach enables precise control over peptide sequence, length,

and modifications, producing well-defined peptide products. Both approaches are widely employed and, depending on the use and level of specificity required, each can complement the other. The peptide mixtures are later divided by chromatographic and electrophoretic methods to get individual peptides. Usually, subsequent peptide identification and characterization are done by mass spectrometry that is coupled with bioinformatics tools, which enable the detailed analysis of the peptide sequences and properties. Through a variety of bioactivity validation assays, such as biochemical, in vitro , in silico , and cell-based approaches, the functional significance of these peptides is ultimately demonstrated. The integrated workflow shows how processing and analytical steps together allow systematic discovery, identification, and evaluation of bioactive peptides from complex biological systems. These techniques are often time-consuming and are being combined with computation to increase speed to discovery. Technologies like in silico digestion, peptide databases, proteomic tools, molecular docking, and QSAR-based prediction tools offer speedy screening of extensive peptide libraries and help identify the most likely candidates before experimental validation.