Study On The Effect Of Copper Peptide And Phenolic Compounds On Tyrosinase

Tyrosinase is the key enzyme in melanin synthesis.Abnormal synthesis of tyrosinase in human may lead to vitiligo chloasma melanoma and other diseases,which seriously affect people’s lives.Tyrosinase inhibitors and activators are now widely used in beauty and medicine.This paper is divided into three parts:The first part is the introduction about the tyrosinase,the melanin,the Glycyl-histidyl-lysine（GHK）-Cu and the Polylactic-co-glycolicde（PLGA）nano-particles,the recent advances in tyrosinase inhibitors and activators.GHK-Cu is a complex of glycyl histidine tripeptide with copper.It has multiple biological activities.In the second part,PLGA has been used as carrier for encapsulating GHK-Cu to prepare GHK-Cu-PLGA nanoparticles and the effects of tyrosinase and melanogenesis in melanocyte were analyzed.The results showed that GHK-Cu could activate mushroom tyrosinase.The entrapment efficiency of GHK-Cu-PLGA nanoparticles was40.12%,and particle size was 100-200nm.Round with uniform size particles were observed under transmission electron microscope.GHK-Cu-PLGA nanoparticles were successfully delivered GHK-Cu into melanocyte,stimulated tyrosinase and increased melanogenesis.Our results provide the evidence that GHK-Cu-PLGA nanoparticles could be utilized as a treatment for hypomelanosis or depigmentation disorder.Phenols have a good inhibitory effect on tyrosinase.The third part of this paper is guided by the principle of patching in the design of new drugs.Coupling of a leading compound（catechol,resorcinol,hydroquinone）hydroxyl or other groups with a bioactive compound（galactose,glucoside,or other group）directly or indirectly.Several phenolic derivatives were designed and synthesized as candidate compounds,and the tyrosine inhibitory activity of the candidate compounds was detected.The results showed that:Among the synthetic derivatives of catechol,A3、A7、A8、A9、A10、A11、A12、A13、A14 showed inhibitory effect on tyrosinase,and A3 had the best effect on tyrosinase;Among the synthesized resorcinol derivatives,B2、B3、B6、B7、B8、B9、B10、B11、B12、B13、B14 showed an inhibitory effect on tyrosinase,and B13 was the best;In the synthesis of hydroquinone derivatives,C1、C3、C5、C7、C13、C14、C15、C16、C17、C18、C19、C20、C23、C24、C25、C28、C29、C30、C31、C33、C34 showed inhibitory effects on tyrosinase,and C5、C23、C24、C25、C33、C34 had significant effects.The cytotoxicity of the phenolic derivatives with high activity were evaluated.The results showed that the concentration of tyrosinase semi-inhibitory concentration(IC₅₀)was 20 times less than that of hepatotoxicity.