Design,Screening And Mechanism Of Melanogenesis Inhibiting Peptides

Melanin is a kind of polymer complex that synthesized by tyrosinase-catalyzed oxidation in melanocytes.The content and distribution of melanin determine the color of the skin.Although melanin in the skin protects cells from UV-induced DNA damage,abnormal production and accumulation of melanin can lead to some common pigmentary disorders,including sunburn,melasma,and post-inflammatory skin pigmentation,even the occurrence of melanoma.These are serious aesthetic and health problems for people.Therefore,how to prevent and treat hyperpigmentation of the skin has become an important issue in this field,with great use value and economic value.Compared to natural plant ingredients and synthetic melanin inhibitors with many adverse reactions,short peptide inhibitors have received more and more attention in recent years due to their high performance,low toxicity and other characteristics.But the poor transdermal bioavailability greatly limits its clinical and commercial applications compared to chemical small molecules.In this study,we first analyzed the structure-activity relationship of peptide melanin inhibitors,and then selected five of the most advanced peptide from the laboratory established antioxidant peptide library as templates to design a series of modified short peptide inhibitors.Subsequently,through the screening of a variety of pharmacodynamics and toxicological experiments in vitro and guinea pig skin melanin deposition inhibition models in vivo,the best candidate short peptide Ansin-2(TRCFRVCS)was finally obtained,which contains only8 amino acid residues.Ansin-2 has strong antioxidant activity,can effectively inhibit the cellular tyrosinase activity and melanin content,and local small doses can prevent or even repair UVB-induced guinea pig skin pigmentation.Discovered in the study of the mechanism of Ansin-2,Ansin-2 significantly inhibited the melanin synthesis in B16 melanoma cells by regulating the MITF and subsequently TYR production.Besides,molecular docking and LIGPLOT studies reveals that Ansin-2 was well positioned in the catalytic site of TYR,which in turn inhibits the melanin biosynthesis.Additionally,unlike other hydrophilic and peptidic drug that needs delivering system across the skin,Ansin-2 can be topical delivered efficiently to cells of the epidermis and dermis per se without affiliated moiety.Given that Ansin-2 lacked the unwanted toxicities(hemolysis,cytotoxicity and mast cell degranulation),Ansin-2 could be a safe and promising agent applicable in the situation of skin hyperpigmentation disorders from cosmetics to thepharmaceutical industry,can be used to prevent,reduce and treat skin melanin hyperpigmentation.