School of Life Science and Biotechnology , Dalian University of Technology , Dalian , Liaoning 116024 , China.
Department of Pharmaceutical Sciences, College of Pharmaceutical Sciences , Soochow University , Suzhou , Jiangsu 215123 , China.
J Med Chem. 2018 Aug 9;61(15):6846-6857. doi: 10.1021/acs.jmedchem.8b00737. Epub 2018 Jul 27.
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.
皮肤黑色素生成过多导致的色素沉着过度会引起严重的色素紊乱，甚至黄褐斑。由于短肽（SPs）在皮肤病治疗方面具有潜在的疗效，且全身副作用较低，因此最近引起了人们的关注。在这里，我们展示了一种八肽，Ans in2，是从头设计的，来自我们之前报道的抗氧化 SPs，通过调节 MITF 途径减少酪氨酸酶的产生，从而显著抑制 B16 细胞中的黑色素生成。Ans in2 还可以通过覆盖其催化口袋来抑制酪氨酸酶的功能，这在对接和 LIGPLOT 研究中得到了模拟。Ans in2 的局部应用在豚鼠模型的 UVB 诱导色素沉着中表现出明显的保护作用，无论是预防还是治疗。有趣的是，与其他需要输送系统的亲水性和亲肽性药物不同，Ans in2 可以本身有效地局部输送到表皮和真皮中，而无需附属部分。鉴于 Ans in2 缺乏不良毒性和免疫原性，它在化妆品和制药行业治疗色素沉着过度方面具有很大的潜力。
