Synthesis of cyclic peptides with antioxidant and skin-lightening properties

Purpose Cyclic peptides have emerged as a compelling class of therapeutic and bioactive compounds owing to their diverse and potent biological activities. Nevertheless, their commercialization has been hindered by considerable challenges in synthesis and elevated cost of production. Methods In this study, we employed a scalable and cost-effective chemical synthesis strategy to rapidly design and synthesize a linear peptide sequence with antioxidant and skin-lightening properties using solid-phase peptide synthesis (SPPS). Subsequently, the cyclic peptides Cys-Tyr-Gly-Ser-Arg (CR5) was developed using liquid-phase peptide synthesis (LPPS). Results The cytotoxicity of CR5 was evaluated via the WST-1 assay, revealing over 90% cell viability at concentrations up to 400 µg/mL, indicative of high cellular biocompatibility. Moreover, CR5 demonstrated more than 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity with an IC₅₀ of 16.62 µg/mL, highlighting its notable antioxidant efficacy. In addition, CR5 showed 97.79% tyrosinase inhibition at 800 µg/mL, with an IC₅₀ of 30.77 µg/mL, confirming its strong skin-lightening potential. Conclusion The cyclic peptide CR5 developed in this study has high production scalability and dual functional properties in the form of antioxidant and skin-lightening activities. It is a promising candidate for future applications in the pharmaceutical and cosmetic industries.