Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea.
Ruby Crown Co., Ltd., Suite 505, Korea, Mediventure Center, 76 Dongnae-ro, Dong-gu, Daegu, 41061, Republic of Korea.
Br J Dermatol. 2019 Jul;181(1):128-137. doi: 10.1111/bjd.17634. Epub 2019 Apr 1.
Antimelanogenic peptides are potentially useful to treat hyperpigmentation, but many peptides have limited application because of high cost and/or low activity.
To identify small and potent peptide inhibitors of cellular melanin synthesis that are useful for cosmetic and medical applications.
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).
Predicted active tetrapeptide sequences were R-(F/L)-(C/W)-(G/R)-NH . Of the individual tetrapeptides tested, D3 (RFWG-NH ) and D5 (RLWG-NH ) exhibited high antimelanogenic activities. Tetrapeptide D9 (FRWG-NH ) with a sequence identical to that of a portion of α-MSH also showed antimelanogenic activity. Of the tripeptides tested, E5 (FWG-NH ), E6 (LWG-NH ) and E7 (RWG-NH ) were relatively more active. Dipeptide F1 (WG-NH ) and monopeptide G1 (G-NH , glycinamide) retained activity, but G2 (Ac-G-NH ) 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-NH ·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.
Small peptides, including glycinamide and tryptophanyl glycinamide, are potent antimelanogenic agents with potential value for the treatment of skin hyperpigmentation.
抗黑色素生成肽在治疗色素沉着过度方面具有潜在的应用价值，但由于成本高和/或活性低，许多肽的应用受到限制。
鉴定可用于美容和医学应用的具有细胞黑色素合成抑制活性的小分子、强效肽抑制剂。
使用位置扫描合成四肽组合文库筛选潜在活性肽。用α-促黑素细胞激素（α-MSH）处理 B16-F10 黑素瘤细胞和人表皮黑素细胞，评估肽库和单个肽的抗黑色素生成活性。
预测的活性四肽序列为 R-(F/L)-(C/W)-(G/R)-NH 。在所测试的单个四肽中，D3（RFWG-NH ）和 D5（RLWG-NH ）表现出高的抗黑色素生成活性。序列与 α-MSH 部分序列相同的四肽 D9（FRWG-NH ）也表现出抗黑色素生成活性。在所测试的三肽中，E5（FWG-NH ）、E6（LWG-NH ）和 E7（RWG-NH ）相对更具活性。二肽 F1（WG-NH ）和单肽 G1（G-NH ，甘氨酰胺）保留活性，但 G2（Ac-G-NH ）和 G3（甘氨酸）没有。肽 D3、E5、F1 和 G1 的抗黑色素生成活性在 α-MSH 刺激的人表皮黑素细胞中得到验证。市售的 G-NH·HCl 抑制 cAMP 反应元件结合蛋白的磷酸化水平、小眼畸形相关转录因子和酪氨酸酶的蛋白水平、酪氨酸酶的 l-酪氨酸羟化酶活性以及刺激细胞中的黑色素水平。
包括甘氨酰胺和色氨酰甘氨酰胺在内的小肽是强效的抗黑色素生成剂，具有治疗皮肤色素沉着过度的潜在价值。
