In Vitro and In Silico Evaluation of a Novel Multifunctional Cyclic Peptide with Antioxidant, Tyrosinase-Inhibitory, and Extracellular Matrix-Modulating Activities

Peptides are notable cosmetic ingredients owing to their diverse biological activities and beneficial effects on skin health. Therefore, multifunctional peptides capable of simultaneously exerting antioxidant, whitening, and anti-wrinkle effects are highly desirable. In this study, a scalable and cost-effective chemical synthesis strategy was used for the rapid design and synthesis of linear peptide sequences with skin bioactivity using solid-phase peptide synthesis. Subsequently, liquid-phase peptide synthesis was used to enhance the proteolytic stability and develop a cyclic peptide, cyclic CYGSR (CR5), which was subjected to in vitro biological evaluation. CR5 showed high biocompatibility in water-soluble tetrazolium salt-1 (WST-1) assays, maintaining over 90% cell viability at concentrations up to 400 μg/mL. In the 2,2-Diphenyl-1-picrylhydrazy (DPPH) assay, CR5 exhibited strong antioxidant activity with 83.18% radical scavenging at 200 μg/mL. It also showed 97.79% tyrosinase inhibition at 800 μg/mL, confirming significant whitening potential. Moreover, CR5 inhibited matrix metalloproteinase-1 (MMP-1) expression by 73.55% and increased type I procollagen expression by 44.68% at 400 μg/mL, demonstrating its anti-wrinkle potential. Additionally, molecular docking and dynamic simulation demonstrated stable binding of the peptide to tyrosinase and MMP-1. Collectively, CR5 possesses multifunctional properties with excellent biocompatibility, highlighting its potential as a novel cosmetic active ingredient.