Rational Design of PCR12mod6, a Cathelicidin-HR-Derived Peptide with Enhanced Dual-Action Antimicrobial and...

The escalating threat of antibiotic resistance demands novel antimicrobial strategies. This study introduces PCR12mod6, a rationally designed peptide derived from the amphibian Hoplobatrachus rugulosus cathelicidin-HR, engineered for both antimicrobial and antioxidant functions. PCR12mod6 was optimized through computational modeling and sequence modifications, incorporating lysine and tryptophan to enhance positive charge, amphipathicity, and membrane interactions. In vitro assays corroborated improved broad-spectrum antimicrobial activity and radical scavenging ability in ABTS and DPPH assays compared to those of its parent peptide, PCR12. Furthermore, PCR12mod6 demonstrated significant cytoprotective effects against H₂O₂-induced oxidative stress in RAW 264.7 macrophages and exhibited anti-inflammatory properties by reducing nitric oxide production. Molecular docking suggests that PCR12mod6 interacts with key proteins involved in oxidative stress and inflammation, including Keap1, MD-2, and iNOS. These findings position PCR12mod6 as a promising dual-function therapeutic candidate for combating both antimicrobial resistance and oxidative stress-related disorders.