Identification of small peptides and glycinamide that inhibit melanin synthesis using a positional scanning synthetic peptide combinatorial library.

Abstract

BACKGROUND:

Antimelanogenic peptides are potentially useful to treat hyperpigmentation, but many peptides have limited application because of high cost and/or low activity.

OBJECTIVES:

To identify small and potent peptide inhibitors of cellular melanin synthesis that are useful for cosmetic and medical applications.

METHODS:

A positional scanning synthetic tetrapeptide combinatorial library was used for screening of potentially active peptides. Antimelanogenic activities of the peptide pools and individual peptides were evaluated in B16-F10 melanoma cells and human epidermal melanocytes treated with alpha-melanocyte-stimulating hormone (α-MSH).

RESULTS:

Predicted active tetrapeptide sequences were R-(F/L)-(C/W)-(G/R)-NH2 . Of the individual tetrapeptides tested, D3 (RFWG-NH2 ) and D5 (RLWG-NH2 ) exhibited high antimelanogenic activities. Tetrapeptide D9 (FRWG-NH2 ) with a sequence identical to that of a portion of α-MSH also showed antimelanogenic activity. Of the tripeptides tested, E5 (FWG-NH2 ), E6 (LWG-NH2 ) and E7 (RWG-NH2 ) were relatively more active. Dipeptide F1 (WG-NH2 ) and monopeptide G1 (G-NH2 , glycinamide) retained activity, but G2 (Ac-G-NH2 ) and G3 (glycine) did not. The antimelanogenic activities of peptides D3, E5, F1 and G1 were verified in α-MSH-stimulated human epidermal melanocytes. Commercially available G-NH2 ·HCl suppressed the phosphorylation levels of cAMP-responsive element binding protein, protein levels of microphthalmia-associated transcription factor and tyrosinase, l-tyrosine hydroxylase activity of tyrosinase, and the melanin levels in stimulated cells.

CONCLUSIONS:

Small peptides, including glycinamide and tryptophanyl glycinamide, are potent antimelanogenic agents with potential value for the treatment of skin hyperpigmentation.

• Authors: J H Kim, J K Seok, Y M Kim, Y C Boo
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 181 Issue 1 Pg. 128-137 (07 2019) ISSN: 1365-2133 [Electronic] England
• PMID: 30637717 (Publication Type: Journal Article)
• Copyright: © 2019 British Association of Dermatologists.

Chemical References

• Dermatologic Agents
• Dipeptides
• Melanins
• Peptide Library
• glycine amide
• alpha-MSH
• tryptophylglycine
• Glycine

Topics

• Animals
• Cell Line, Tumor
• Dermatologic Agents (chemical synthesis, pharmacology, therapeutic use)
• Dipeptides (chemical synthesis, pharmacology, therapeutic use)
• Glycine (analogs & derivatives, chemical synthesis, pharmacology, therapeutic use)
• Humans
• Hyperpigmentation (drug therapy)
• Melanins (antagonists & inhibitors, biosynthesis)
• Melanocytes (drug effects, metabolism)
• Mice
• Peptide Library
• alpha-MSH (metabolism)