De Novo Molecular Design of a Novel Octapeptide That Inhibits In Vivo Melanogenesis and Has 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, designed de novo from antioxidant SPs we previously reported,
significantly inhibiting melanogenesis in B16 cells by decreasing
tyrosinase production via regulating the MITF pathway. Ansin2 could
also inhibit tyrosinase function by covering its catalytic pocket,
which was simulated in docking and LIGPLOT studies. Topical application
of ansin2 exhibited evident protection in UVB-induced pigmentation
in guinea pig models both in terms of prophylaxis and treatment. Interestingly,
unlike other hydrophilic and peptidic drugs that need delivery systems,
ansin2 can be efficiently delivered topically to the epidermis and
dermis per se without an affiliated moiety. Given that ansin2 lacks
unwanted toxicities and immunogenicity, it holds great potential in
treating hyperpigmentation in the cosmetics and pharmaceutical industries.