Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing

Cathelicidins are a class of gene-encoded multifunctional factors in host defence systems. They have recently attracted a great deal of attention as promising drug candidates. Cathelicidins are well studied in vertebrates, yet no studies have been reported concerning gecko cathelicidin. Recently, we identified a novel cathelicidin from Gekko japonicus, Gj-CATH3. Unlike most cathelicidins, Gj-CATH3 exhibits potent antioxidant activity in vitro. Unfortunately, slight toxicity and high synthesis cost restrict its application. Thus, we designed a series of Gj-CATH3 analogues for development of short Peptides with improved cell selectivity. Functional analysis showed that two truncated Peptides, Gj-CATH3-(38-42)-peptide and Gj-CATH3-(33-42)-peptide, exhibited excellent antioxidant activity against ABTS and DPPH free radicals. Further, cytotoxicity and hemolytic activities were observably lower compared to Gj-CATH3. Interestingly, both Peptides also demonstrate significant wound healing properties in a mouse model with full-thickness skin wounds. The Peptides induce HaCaT cell proliferation and prevent decreases in SOD activity and increases of MDA concentration in injured-skin tissue. This report is the first to address cathelicidin from reptilia that exhibit potent wound healing activity. Our research will enrich understanding of cathelicidin biological functions, and provide a theoretical basis for its clinical application.