Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

Tseng, Tien‐Sheng; Tsai, Keng‐Chang; Chen, Wang-Chuan; Wang, Yeng‐Tseng; Lee, Yu-Ching; Lu, Chung-Kuang; Don, Ming‐Jaw; Chang, Chang‐Yu; Lee, Ching-Hsiao; Lin, Hui-Hsiung; Hsu, Hung-Ju; Hsiao, Nai-Wan

doi:10.1021/acs.jafc.5b01026

Cited by 35 publications

(33 citation statements)

References 49 publications

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“…CRY and RCY used the thiol group of the cysteine residue to coordinate with Cu ions at the active site of tyrosinase, thereby showing low tyrosinase activity. In another study, the cysteine-containing dipeptides were reported to inhibit the tyrosinase activity in an effective manner 110 . The authors suggested that these cysteine-containing dipeptides could directly block the active site of tyrosinase and thereby leading to potent inhibition.…”

Section: Mushroom Tyrosinase Inhibitorsmentioning

confidence: 99%

Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors

Pillaiyar

Manickam

Namasivayam

2017

Journal of Enzyme Inhibition and Medicinal Chemistry

676

489

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Melanogenesis is a process to synthesize melanin, which is a primary responsible for the pigmentation of human skin, eye and hair. Although numerous enzymatic catalyzed and chemical reactions are involved in melanogenesis process, the enzymes such as tyrosinase and tyrosinase-related protein-1 (TRP-1) and TRP-2 played a major role in melanin synthesis. Specifically, tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin synthesis, and the downregulation of tyrosinase is the most prominent approach for the development of melanogenesis inhibitors. Therefore, numerous inhibitors that target tyrosinase have been developed in recent years. The review focuses on the recent discovery of tyrosinase inhibitors that are directly involved in the inhibition of tyrosinase catalytic activity and functionality from all sources, including laboratory synthetic methods, natural products, virtual screening and structure-based molecular docking studies.

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Section: Mushroom Tyrosinase Inhibitorsmentioning

confidence: 99%

Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors

Pillaiyar

Manickam

Namasivayam

2017

Journal of Enzyme Inhibition and Medicinal Chemistry

676

489

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“…It may also be related to Parkinson’s disease and cancer. 4,7 Thus, tyrosinase inhibition is of interest in the food, medicine and cosmetics fields.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Identification of Tyrosinase-Inhibitory and Copper-Chelating Peptides from Hydrolyzed Rice-Bran-Derived Albumin

Kubglomsong

Theerakulkait

Reed

et al. 2018

J. Agric. Food Chem.

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Rice-bran albumin (RBAlb), which shows higher tyrosinase-inhibitory activity than other protein fractions, was hydrolyzed with papain to improve the bioactivity. The obtained RBAlb hydrolysate (RBAlbH) was separated into 11 peptide fractions by RP-HPLC. Tyrosinase inhibition and copper chelation activities decreased with increasing retention times of the peptide fractions. RBAlbH fraction 1, which exhibited the greatest activity, contained 13 peptides whose sequences were determined by using LC-MS/MS. Most of the peptide sequences contained features of previously reported tyrosinase-inhibitory and metal-chelating peptides, especially peptide SSEYYGGEGSSSEQGYYGEG. RBAlbH fraction 1 showed more effective tyrosinase inhibition (IC = 1.31 mg/mL) than citric acid (IC = 9.38 mg/mL), but it was less effective than ascorbic acid (IC = 0.03 mg/mL, P ≤ 0.05). It showed copper-chelating activity (IC = 0.62 mg/mL) stronger than that of EDTA (IC = 1.06 mg/mL, P ≤ 0.05). These results suggest that RBAlbH has potential as a natural tyrosinase inhibitor and copper chelator for application in the food and cosmetic industries.

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“…L -Tyr was stimulatory, while D -Tyr and L -Cys were inhibitory to melanin synthesis in cells [ 76 , 84 , 92 ]. Many Cys-containing compounds, such as glutathione, inhibited TYR-catalyzed melanin synthesis by acting as a reactant for the thiol conjugation reaction with DOPAquinone as well as acting as an enzyme inhibitor [ 87 , 88 , 89 ]. A number of peptides from synthetic peptide libraries or natural sources exhibited inhibitory effects against TYR activity in vitro, and some showed antimelanogenic effects at the cell level [ 90 , 101 , 102 , 103 , 104 ].…”

Section: Discussionmentioning

confidence: 99%

“…Dipeptides GD, GK, and GH diminished the browning of fresh Golden Delicious apples and Irish White Skinned potatoes. Tseng et al estimated the inhibitory capacity of 20 × 20 dipeptides against mushroom TYR [ 87 ]. Cys-containing dipeptides exhibited highly potent TYR inhibition, and N-terminal Cys-containing dipeptides, such as CE (IC 50 = 2.0 μM), outperformed C-terminal Cys-containing dipeptides.…”

Section: Artificial Downregulation Of Melanin Synthesismentioning

confidence: 99%

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

Boo

2020

Biomedicines

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Harmonious synthesis and distribution of melanin in the skin contribute to the expression of beauty and the maintenance of health. When skin pigmentary disorders occur because of internal or external factors or, when there is a need to artificially increase or reduce the pigmentation level of the skin for aesthetic or therapeutic purposes, various pharmacological therapies are applied but the results are not always satisfactory. Studies have been conducted to improve the efficacy and safety of these treatment strategies. In this review, we present the latest studies regarding peptides and related compounds that may be useful in artificially increasing or reducing skin melanin levels. Certain analogs of α-melanocyte stimulating hormone (MSH) and oligopeptides with the sequences derived from the hormone were shown to promote melanin synthesis in cells and in vivo models. Various amino acids, peptides, their analogs, and their hybrid compounds with other chemical moieties were shown to inhibit tyrosinase (TYR) catalytic activity or downregulate TYR gene expression. Certain peptides were shown to inhibit melanosome biogenesis or induce autophagy, leading to decreased pigmentation. In vivo and clinical evidence are available for some compounds, including [Nle4-D-Phe7]-α-MSH, glutathione disulfide, and glycinamide hydrochloride. For many other compounds, additional studies are required to verify their efficacy and safety in vivo and in clinical trials. The accumulating information regarding pro- and antimelanogenic activity of peptides and related compounds will lead to the development of novel drugs for the treatment of skin pigmentary disorders.

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Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

Cited by 35 publications

References 49 publications

Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors

Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors

Isolation and Identification of Tyrosinase-Inhibitory and Copper-Chelating Peptides from Hydrolyzed Rice-Bran-Derived Albumin

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

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