Identification of novel antimelanogenic hexapeptides via positional scanning of a synthetic peptide combinatorial library

Seok, Jin Kyung; Lee, Seok Won; Choi, Jaehyuk; Kim, Young Mi; Boo, Yong Chool

doi:10.1111/exd.13262

Cited by 6 publications

(20 citation statements)

References 11 publications

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“…Our recent studies identified certain low molecular anti-melanogenic peptides [26,27]. In these studies, a special algorithm was used to predict the sequences of active peptides using a positional scanning synthetic peptide combination library [28,29].…”

Section: Introductionmentioning

confidence: 99%

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

Boo

Jo²,

et al. 2020

Biomedicines

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A previous study identified certain low molecular anti-melanogenic peptides that share a common sequence with α-melanocyte stimulating hormone (MSH) and end with a glycinamide moiety. Glycinamide itself also showed anti-melanogenic activity in cell-based assays, but neither glycine nor acetyl glycinamide were active, which indicated a special structure and activity relationship. The aim of this study was to examine the skin depigmentation efficacy of glycinamide hydrochloride in human subjects. The primary skin irritation potential of glycinamide hydrochloride was evaluated by patch testing in 30 human subjects. The skin depigmentation efficacy of glycinamide hydrochloride was evaluated in a double-blinded clinical test in 21 human subjects. The test product and a control product were applied to designated sites on the right or left side of the face twice daily for eight weeks. Skin color parameters, i.e., the melanin index, the L* value (representing skin lightness), a* value (redness), and b* value (yellowness) were measured using instruments. The individual topology angle (ITAo, representing skin color) was calculated from L* and b values. The degree of skin pigmentation was visually assessed by two testers. The primary skin irritation test showed that a solution containing glycinamide hydrochloride up to 10% did not induce any adverse skin responses. In the efficacy test, the test product significantly reduced the melanin index, and increased L* value and ITAo after two weeks of application relative to the baseline value at the start of the test. It also significantly lowered the degree of pigmentation after 6 weeks of application, relative to the baseline value. Differences in the melanin index, L* value, ITAo and the degree of pigmentation between the test and control groups became statistically significant after six weeks or eight weeks of application. No signs of skin irritation were observed during the efficacy test. The present study suggests that glycinamide hydrochloride has great potential to be used in the control of skin hyperpigmentation.

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Section: Introductionmentioning

confidence: 99%

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

Boo

Jo²,

et al. 2020

Biomedicines

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“…In a study of marine plants, it was reported that the extract of Phyllospadix iwatensis and its active ingredient, luteolin 7-sulfate, inhibited cell melanin production by inhibition of TYR gene expression as well as inhibition of TYR catalytic activity [47,48]. Recently, by applying the peptide library screening method, we found low molecular peptides that inhibit cell melanin production [49,50]. These peptides share the common sequence with α-MSH and thus can act as an antagonist of MC1R which are involved in the regulation of TYR gene expression [50].…”

Section: Discussionmentioning

confidence: 99%

“…The intracellular melanin retained in cells and extracellular melanin secreted from cells were separately determined [49,57]. B16-F10 cells were plated in 6-well plates (1.2 × 10 4 cells per well), cultured for 24 h, treated with a test drug at various concentrations for 60 min, and stimulated with 100 nM α-MSH for 72 h. The conditioned medium was evaluated to determine the extracellular melanin content.…”

Section: Melanin Content Assaymentioning

confidence: 99%

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Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms

Song

Hwang

et al. 2020

IJMS

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The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1–1.5 µM) as compared to β-arbutin (IC50, 500–700 µM) or kojic acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders

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“…6). The hexapeptide, FSHHLG (HP), is known to attenuate melanin synthesis 23 . However, under our experimental conditions, the addition of D-tyrosine to HP at the C-terminus (HP-D) showed no additional effect on melanin synthesis in MNT-1 cells (Fig.…”

Section: D-tyrosine Confers An Anti-melanogenic Effect To Short Cosmementioning

confidence: 99%

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

Park

Jung²,

Jang

et al. 2020

Sci Rep

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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...

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Identification of novel antimelanogenic hexapeptides via positional scanning of a synthetic peptide combinatorial library

Cited by 6 publications

References 11 publications

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms

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

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