Synthesis and In Vitro Evaluation of a Novel Tyrosinase-Targeting Cyclic Peptide with Radical Scavenging Activity

Excessive melanin production causes various pigmentary disorders, and strategies involving tyrosinase inhibition and antioxidant activity are crucial for regulating this process.

In this study, we designed and synthesized CV5, a short head-to-tail cyclic peptide, and evaluated its structural characteristics and biological activity.

CV5 exhibited excellent biocompatibility with a purity of over 98% and no cytotoxicity. Furthermore, it exhibited tyrosinase inhibitory activity approximately 1.6 times higher than that of arbutin (IC₅₀: 336.7 ± 5.79 µM) and demonstrated antioxidant effects that were 1.6-fold and 1.8-fold superior to the two control groups in DPPH and ABTS radical scavenging assays, respectively (IC₅₀: 30.27 ± 1.06 µM, 282.4 ± 11.45 µM). Molecular docking analysis confirmed the potential for interaction with the enzyme’s active site.

These results suggest that a natural amide-based cyclization strategy can overcome the biocompatibility and metabolic limitations associated with peptidomimics incorporating non-natural skeletons, and validate CV5 as a potential candidate for the treatment of pigmentary disorders and the promotion of skin health.