Structural Basis and Applications of Antioxidant Peptides in Mitigating Oxidative Damage

Antioxidant peptides (APs) effectively neutralize free radicals and attenuate oxidative stress-related pathologies. However, the structural and conformational determinants underlying their bioactivity remain underexplored. In this study, six APs (AP1–AP6) with the sequence CKC- X -WM were designed, where X represents amino acid residues with distinct physicochemical properties. Quantum chemical calculations and molecular docking elucidated how residue-specific modulation influences redox activity and intermolecular interactions. AP2 and AP4 exhibited superior in vitro and cellular antioxidant capacities, attributed to their optimized orbital energy gaps (4.894 51 and 4.902 13 eV, respectively). In vivo applications demonstrated their efficacy in alleviating oxidative damage in models of diabetes, aging, UV-induced photodamage, and acute alcoholic hepatotoxicity. Computational methods provided mechanistic insights into conformational dynamics, highlighting the multifunctionality of APs. This study advances the rational design of therapeutic peptides and their potential as functional biomaterials for oxidative stress management.