D-tyrosine adds an anti-melanogenic effect to cosmetic peptides

Abstract

D-tyrosine is known to negatively regulate melanin synthesis by inhibiting tyrosinase activity. Here, we further reveal that peptides containing terminal D-tyrosine can reduce the melanin contents of human melanocytes. the addition of D-tyrosine to the terminus of the commercial anti-wrinkle peptide, pentapeptide-18 endowed the peptide with the ability to reduce the melanin content and tyrosinase activity in human MNT-1 melanoma cells and primary melanocytes. Consistently, terminal D-tyrosine-containing pentapeptide-18 inhibited the melanogenesis induced by α-MSH treatment or UV irradiation of MNT-1 cells and reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Furthermore, the addition of D-tyrosine to an anti-aging peptide (GEKG) or an antiinflammatory peptide (GHK) endowed these short peptides with anti-melanogenic effects without altering their intrinsic effects. Together, these data suggest that the addition of D-tyrosine at the terminus of a short cosmetic peptide adds an anti-melanogenic effect to its intrinsic cosmetic effect. Our work offers a novel means of generating dual-function cosmetic peptides.Melanin synthesis occurs in melanocytes and is an essential physiological process that determines the color of human skin and protects its DNA from UV damage 1 . It is closely related with the occurrence of pigmentary disorders 2 : the imbalanced regulation of melanin synthesis results in many pigmentary skin diseases that commonly affect men and women of all ethnic groups 3 , including hyperpigmentation disorders, such as melanocytic nevus, seborrheic keratosis, and melanoma, and hypopigmentation disorders, such as piebaldism, pityriasis, and vitiligo.Melanin is synthesized in melanosomes, which are transferred to surrounding keratinocytes where they protect cells against DNA damage 4,5 . Melanogenesis is critically regulated by the expression of various melanogenesis-related enzymes, such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). Tyrosinase, the rate-limiting enzyme for controlling melanin synthesis, is involved primarily in the production of L-dopaquinone 5,6 . TRP-1 and TRP-2 catalyze specific steps in melanogenesis and stabilize tyrosinase activity 7 . As tyrosinase is a key enzyme that catalyzes a rate-limiting step of melanin synthesis, numerous inhibitors that target tyrosinase have been investigated for their ability to inhibit this process. These include well-known tyrosinase inhibitors, such as hydroquinone 8 , arbutin 9 , kojic acid 10 , and salicylic acid 11 . However, due to the side effects of these inhibitors and the increasing demand for safe and effective cosmetics, many continuing efforts are being made to identify or produce new skin-whitening agents. Some researchers have screened natural products and found that chalcones, resveratrol, and coumarins exhibit inhibitory activity against mushroom tyrosinase 12 . Other groups have sought to develop bioactive materials. Particular attention has been paid to vario...

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

“…Then, successive chemical reactions are triggered until melanin is completely formed [ 11 , 12 ]. Due to its determinant role in the biosynthetic pathway of melanin, tyrosinase has been widely investigated as an interesting molecular target with applications in the pharmaceutical and cosmetic industries [ 13 , 14 , 15 , 16 , 17 ].…”

Advances in D-Amino Acids in Neurological Research

“…D-Tyrosine has no established activity in the brain but has recently been shown to be effective as a tyrosinase inhibitor, preventing melanin formation [ 22 , 56 ]. This is particularly interesting as tyrosinase has been implicated in neurodegenerative diseases such as Parkinson’s Disease [ 126 , 127 ].…”

Up- or Downregulation of Melanin Synthesis Using Amino Acids, Peptides, and Their Analogs

“…Treatment with 10 mM D -Tyr reduced melanin synthesis in the epidermal basal layer of a 3D human skin model [ 92 ]. In a subsequent study, this research group demonstrated that the addition of a D -Tyr residue to the C-terminus of certain functional peptides could increase their TYR inhibitory activity in vitro and antimelanogenic activity in cells, while retaining the intrinsic properties of the unmodified peptides [ 93 ].…”