De novo Molecular Design of Novel Octapeptide that Inhibits In Vivo Melanogenesis with Great Transdermal Ability

Cutaneous hyperpigmentation from excess melanogenesis causes serious pigmentary disorders and even melasma. Short peptides (SPs) are garnering attention lately owing to their therapeutic potential in dermatological diseases and low systemic side-effects. Here, we show an octapeptide, Ansin2, de novo designed from antioxidant SPs we previously reported, significantly inhibited the melanogenesis in B16 cells by decreasing the tyrosinase production via regulating MITF pathway. Ansin2 could also inhibit the tyrosinase function by covering its catalytic pocket, simulated by docking and LIGPLOT studies. Topical application of Ansin2 exhibited evident protection in UVB-induced pigmentation in guinea pig models both in the prophylaxis and treatment way. Interestingly, unlike other hydrophilic and peptidic drug that needs delivering system, Ansin2 can be topical delivered efficiently to the epidermis and dermis per se without affiliated moiety. Given that Ansin2 lacked the unwanted toxicities and immunogenicity, i...