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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of melanin cause hyperpigmentation and neurodegenerative diseases. Thus, tyrosinase is promising for use in medicine and cosmetics. Our previous study identified a natural product, A5, resembling the structure of the dipeptide WY and apparently inhibiting tyrosinase. Here, we comprehensively estimated the inhibitory capability of 20 × 20 dipeptides against mushroom tyrosinase. We found that cysteine-containing dipeptides, directly blocking the active site of tyrosinase, are highly potent in inhibition; in particular, N-terminal cysteine-containing dipeptides markedly outperform the C-terminal-containing ones. The cysteine-containing dipeptides, CE, CS, CY, and CW, show comparative bioactivities, and tyrosine-containing dipeptides are substrate-like inhibitors. The dipeptide PD attenuates 16.5% melanin content without any significant cytotoxicity. This study reveals the functional role of cysteine residue positional preference and the selectivity of specific amino acids in cysteine-containing dipeptides against tyrosinase, aiding in developing skin-whitening products. © 2015 American Chemical Society.
Original languageEnglish
Pages (from-to)6181-6188
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume63
Issue number27
DOIs
Publication statusPublished - 2015

Fingerprint

dipeptides
Monophenol Monooxygenase
Dipeptides
Cysteine
cysteine
Melanins
melanin
Neurodegenerative diseases
Hyperpigmentation
Cosmetics
dopachrome
Agaricales
neurodegenerative diseases
Cytotoxicity
cosmetics
Bioactivity
Biological Products
active sites
Neurodegenerative Diseases
mushrooms

Keywords

  • dopachrome
  • eumelanin formation
  • melanin
  • molecular docking
  • peptide
  • tyrosinase
  • Amino acids
  • Melanin
  • Neurodegenerative diseases
  • Eumelanins
  • Hyperpigmentation
  • Melanin synthesis
  • Molecular docking
  • Mushroom tyrosinase
  • Substrate-like inhibitors
  • Peptides
  • Basidiomycota
  • cysteine
  • dipeptide
  • enzyme inhibitor
  • indole derivative
  • monophenol monooxygenase
  • Agaricales
  • antagonists and inhibitors
  • biosynthesis
  • cell line
  • chemistry
  • drug screening
  • enzymology
  • human
  • kinetics
  • melanocyte
  • metabolism
  • Cell Line
  • Cysteine
  • Dipeptides
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors
  • Humans
  • Indolequinones
  • Kinetics
  • Melanins
  • Melanocytes
  • Molecular Docking Simulation
  • Monophenol Monooxygenase

Cite this

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.

In: Journal of Agricultural and Food Chemistry, Vol. 63, No. 27, 2015, p. 6181-6188.

Research output: Contribution to journalArticle

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. / Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation. In: Journal of Agricultural and Food Chemistry. 2015 ; Vol. 63, No. 27. pp. 6181-6188.
@article{78837ae5de23407993ac08b7b2acda06,
title = "Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation",
abstract = "Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of melanin cause hyperpigmentation and neurodegenerative diseases. Thus, tyrosinase is promising for use in medicine and cosmetics. Our previous study identified a natural product, A5, resembling the structure of the dipeptide WY and apparently inhibiting tyrosinase. Here, we comprehensively estimated the inhibitory capability of 20 × 20 dipeptides against mushroom tyrosinase. We found that cysteine-containing dipeptides, directly blocking the active site of tyrosinase, are highly potent in inhibition; in particular, N-terminal cysteine-containing dipeptides markedly outperform the C-terminal-containing ones. The cysteine-containing dipeptides, CE, CS, CY, and CW, show comparative bioactivities, and tyrosine-containing dipeptides are substrate-like inhibitors. The dipeptide PD attenuates 16.5{\%} melanin content without any significant cytotoxicity. This study reveals the functional role of cysteine residue positional preference and the selectivity of specific amino acids in cysteine-containing dipeptides against tyrosinase, aiding in developing skin-whitening products. {\circledC} 2015 American Chemical Society.",
keywords = "dopachrome, eumelanin formation, melanin, molecular docking, peptide, tyrosinase, Amino acids, Melanin, Neurodegenerative diseases, Eumelanins, Hyperpigmentation, Melanin synthesis, Molecular docking, Mushroom tyrosinase, Substrate-like inhibitors, Peptides, Basidiomycota, cysteine, dipeptide, enzyme inhibitor, indole derivative, monophenol monooxygenase, Agaricales, antagonists and inhibitors, biosynthesis, cell line, chemistry, drug screening, enzymology, human, kinetics, melanocyte, metabolism, Cell Line, Cysteine, Dipeptides, Drug Evaluation, Preclinical, Enzyme Inhibitors, Humans, Indolequinones, Kinetics, Melanins, Melanocytes, Molecular Docking Simulation, Monophenol Monooxygenase",
author = "Tien-Sheng Tseng and Keng-Chang Tsai and Wang-Chuan Chen and Yeng-Tseng Wang and Yu-Ching Lee and Chung-Kuang Lu and Ming-Jaw Don and Chang-Yu Chang and Ching-Hsiao Lee and Hui-Hsiung Lin and Hung-Ju Hsu and Nai-Wan Hsiao",
note = "Export Date: 28 March 2016 CODEN: JAFCA 通訊地址: Hsiao, N.-W.; Institute of Biotechnology, National Changhua University of EducationTaiwan 化學物質/CAS: cysteine, 4371-52-2, 52-89-1, 52-90-4; dopachrome, 3571-34-4; melanin, 8049-97-6; monophenol monooxygenase, 9002-10-2; Cysteine; Dipeptides; dopachrome; Enzyme Inhibitors; Indolequinones; Melanins; Monophenol Monooxygenase 出資詳情: 103-2320-B-077-001-MY3, MOST, Ministry of Science and Technology 出資詳情: MM10211- 0153, MOHW, Ministry of Science and Technology 出資詳情: MM10401-0394, MOHW, Ministry of Science and Technology 參考文獻: Lee, H.E., Kim, E.H., Choi, H.R., Sohn, U.D., Yun, H.Y., Baek, K.J., Kwon, N.S., Kim, D.S., Dipeptides Inhibit Melanin Synthesis in Mel-Ab Cells through Down-Regulation of Tyrosinase (2012) Korean J. Physiol. Pharmacol., 16, pp. 287-291; Brenner, M., Hearing, V.J., The protective role of melanin against UV damage in human skin (2008) Photochem. Photobiol., 84, pp. 539-549; Schallreuter, K., Slominski, A., Pawelek, J.M., Jimbow, K., Gilchrest, B.A., What controls melanogenesis? (1998) Exp. Dermatol., 7, pp. 143-150; Wang, H.M., Chen, C.Y., Wen, Z.H., Identifying melanogenesis inhibitors from Cinnamomum subavenium with in vitro and in vivo screening systems by targeting the human tyrosinase (2011) Exp. Dermatol., 20, pp. 242-248; Lo, C.Y., Liu, P.L., Lin, L.C., Chen, Y.T., Hseu, Y.C., Wen, Z.H., Wang, H.M., Antimelanoma and antityrosinase from Alpinia galangal constituents (2013) Sci. World J., 2013, p. 186505; Iozumi, K., Hoganson, G.E., Pennella, R., Everett, M.A., Fuller, B.B., Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes (1993) J. Invest. Dermatol., 100, pp. 806-811; Chang, T.S., An updated review of tyrosinase inhibitors (2009) Int. J. Mol. Sci., 10, pp. 2440-2475; Seo, S.Y., Sharma, V.K., Sharma, N., Mushroom tyrosinase: Recent prospects (2003) J. Agric. Food Chem., 51, pp. 2837-2853; Passi, S., Nazzaro-Porro, M., Molecular basis of substrate and inhibitory specificity of tyrosinase: Phenolic compounds (1981) Br. J. Dermatol., 104, pp. 659-665; Marusek, C.M., Trobaugh, N.M., Flurkey, W.H., Inlow, J.K., Comparative analysis of polyphenol oxidase from plant and fungal species (2006) J. Inorg. Biochem., 100, pp. 108-123; Katsambas, A.D., Stratigos, A.J., Depigmenting and bleaching agents: Coping with hyperpigmentation (2001) Clin Dermatol, 19, pp. 483-488; Solano, F., Briganti, S., Picardo, M., Ghanem, G., Hypopigmenting agents: An updated review on biological, chemical and clinical aspects (2006) Pigm. Cell Res., 19, pp. 550-571; Asanuma, M., Miyazaki, I., Ogawa, N., Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease (2003) Neurotoxic. Res., 5, pp. 165-176; Pan, T., Li, X., Jankovic, J., The association between Parkinson's disease and melanoma (2011) Int. J. Cancer, 128, pp. 2251-2260; Schurink, M., Van Berkel, W.J., Wichers, H.J., Boeriu, C.G., Novel peptides with tyrosinase inhibitory activity (2007) Peptides, 28, pp. 485-495; Arndt, K.A., Fitzpatrick, T.B., Topical use of hydroquinine as a depigmenting agent (1965) J. Am. Med. Assoc., 194, pp. 117-119; Fitzpatrick, T.B., Arndt, K.A., El-Mofty, A.M., Pathak, M.A., Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo (1966) Arch. Dermatol., 93, pp. 589-600; Germanas, J.P., Wang, S., Miner, A., Hao, W., Ready, J.M., Discovery of small-molecule inhibitors of tyrosinase (2007) Bioorg. Med. Chem. Lett., 17, pp. 6871-6875; Ahn, S.M., Rho, H.S., Baek, H.S., Joo, Y.H., Hong, Y.D., Shin, S.S., Park, Y.H., Park, S.N., Inhibitory activity of novel kojic acid derivative containing trolox moiety on melanogenesis (2011) Bioorg. Med. Chem. Lett., 21, pp. 7466-7469; Elsner, P., Maibach, H.I., (2000) Cosmeceuticals: Drugs Vs. Cosmetics, , Eds. CRC Press: Boca Raton, FL, USA; Breathnach, A.C., Nazzaro-Porro, M., Passi, S., Zina, G., Azelaic acid therapy in disorders of pigmentation (1989) Clin. Dermatol, 7, pp. 106-119; Rigoni, C., Toffolo, P., Serri, R., Caputo, R., Use of a cream based on 20{\%} azelaic acid in the treatment of melasma (1989) G. Ital. Dermatol. Venereol., 124, pp. 1-6; Jimbow, K., N -Acetyl-4- S -cysteaminylphenol as a new type of depigmenting agent for the melanoderma of patients with melasma (1991) Arch. Dermatol., 127, pp. 1528-1534; Hamidian, H., Tagizadeh, R., Fozooni, S., Abbasalipour, V., Taheri, A., Namjou, M., Synthesis of novel azo compounds containing 5(4 H)-oxazolone ring as potent tyrosinase inhibitors (2013) Bioorg. Med. Chem., 21, pp. 2088-2092; Hamidian, H., Synthesis of novel compounds as new potent tyrosinase inhibitors (2013) BioMed Res. Int., 2013, p. 207181; Zhu, T.H., Cao, S.W., Yu, Y.Y., Synthesis, characterization and biological evaluation of paeonol thiosemicarbazone analogues as mushroom tyrosinase inhibitors (2013) Int. J. Biol. Macromol., 62, pp. 589-595; Liang, C., Lim, J.H., Kim, S.H., Kim, D.S., Dioscin: A synergistic tyrosinase inhibitor from the roots of Smilax China (2012) Food Chem., 134, pp. 1146-1148; Zheng, Z.P., Tan, H.Y., Wang, M., Tyrosinase inhibition constituents from the roots of Morus australis (2012) Fitoterapia, 83, pp. 1008-1013; Sarkhail, P., Sarkheil, P., Khalighi-Sigaroodi, F., Shafiee, A., Ostad, N., Tyrosinase inhibitor and radical scavenger fractions and isolated compounds from aerial parts of Peucedanum knappii Bornm (2013) Nat. Prod. Res., 27, pp. 896-899; Lee, Y.C., Hsiao, N.W., Tseng, T.S., Chen, W.C., Lin, H.H., Leu, S.J., Yang, E.W., Tsai, K.C., Phage display-mediated discovery of novel tyrosinase-targeting tetrapeptide inhibitors reveals the significance of N-terminal preference of cysteine residues and their functional sulfur atom (2015) Mol. Pharmacol., 87, pp. 218-230; Chen, W.C., Tseng, T.S., Hsiao, N.W., Lin, Y.L., Wen, Z.H., Tsai, C.C., Lee, Y.C., Tsai, K.C., Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling (2015) Sci. Rep., 5, p. 7995; Abu Ubeid, A., Zhao, L., Wang, Y., Hantash, B.M., Short-sequence oligopeptides with inhibitory activity against mushroom and human tyrosinase (2009) J. Invest. Dermatol., 129, pp. 2242-2249; Upadhyay, A., Chompoo, J., Taira, N., Fukuta, M., Gima, S., Tawata, S., Solid-phase synthesis of mimosine tetrapeptides and their inhibitory activities on neuraminidase and tyrosinase (2011) J. Agric. Food Chem., 59, pp. 12858-12863; Noh, J.M., Kwak, S.Y., Kim, D.H., Lee, Y.S., Kojic acid-tripeptide amide as a new tyrosinase inhibitor (2007) Biopolymers, 88, pp. 300-307; Craik, D.J., Fairlie, D.P., Liras, S., Price, D., The future of peptide-based drugs (2013) Chem. Biol. Drug Des., 81, pp. 136-147; Hsiao, N.W., Tseng, T.S., Lee, Y.C., Chen, W.C., Lin, H.H., Chen, Y.R., Wang, Y.T., Tsai, K.C., Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors (2014) J. Chem. Inf. Model., 54, pp. 3099-3111; Takahashi, M., Takara, K., Toyozato, T., Wada, K., A novel bioactive chalcone of Morus australis inhibits tyrosinase activity and melanin biosynthesis in B16 melanoma cells (2012) J. Oleo Sci., 61, pp. 585-592; Kumar, K.J., Yang, J.C., Chu, F.H., Chang, S.T., Wang, S.Y., Lucidone, a novel melanin inhibitor from the fruit of Lindera erythrocarpa Makino (2010) Phytother. Res., 24, pp. 1158-1165; Wang, K.H., Lin, R.D., Hsu, F.L., Huang, Y.H., Chang, H.C., Huang, C.Y., Lee, M.H., Cosmetic applications of selected traditional Chinese herbal medicines (2006) J. Ethnopharmacol., 106, pp. 353-359; Del Marmol, V., Ito, S., Bouchard, B., Libert, A., Wakamatsu, K., Ghanem, G., Solano, F., Cysteine deprivation promotes eumelanogenesis in human melanoma cells (1996) J. Invest. Dermatol., 107, pp. 698-702; McGregor, D., Hydroquinone: An evaluation of the human risks from its carcinogenic and mutagenic properties (2007) Crit. Rev. Toxicol., 37, pp. 887-914; Philips, N., Burchill, D., O'Donoghue, D., Keller, T., Gonzalez, S., Identification of benzene metabolites in dermal fibroblasts as nonphenolic: Regulation of cell viability, apoptosis, lipid peroxidation and expression of matrix metalloproteinase 1 and elastin by benzene metabolites (2004) Skin Pharmacol. Physiol., 17, pp. 147-152; Charlin, R., Barcaui, C.B., Kac, B.K., Soares, D.B., Rabello-Fonseca, R., Azulay-Abulafia, L., Hydroquinone-induced exogenous ochronosis: A report of four cases and usefulness of dermoscopy (2008) Int. J. Dermatol., 47, pp. 19-23; Ito, S., Ojika, M., Yamashita, T., Wakamatsu, K., Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: Implications for melanocyte toxicity (2014) Pigm. Cell Melanoma Res., 27, pp. 744-753; Daquinag, A.C., Sato, T., Koda, H., Takao, T., Fukuda, M., Shimonishi, Y., Tsukamoto, T., A novel endogenous inhibitor of phenoloxidase from Musca domestica has a cystine motif commonly found in snail and spider toxins (1999) Biochemistry, 38, pp. 2179-2188; Kato, N., Sato, S., Yamanaka, A., Yamada, H., Fuwa, N., Nomura, M., Silk protein, sericin, inhibits lipid peroxidation and tyrosinase activity (1998) Biosci., Biotechnol., Biochem., 62, pp. 145-147; Ates, S., Cokmus, C., Partial characterization of a peptide from honey that inhibits mushroom polyphenol oxidase (2001) J. Food Biochem., 25, pp. 127-137; Okot-Kotber, M., Yong, K.J., Bagorogoza, K., Activity and inhibition of polyphenol oxidase in extracts of bran and other milling fractions from a variety of wheat cultivars (2001) Cereal Chem., 78, pp. 514-520; Chen, M.J., Sheu, J.F., Lin, C.W., Chuang, C.L., Study on skin care properties of milk kefir whey (2006) Asian-Australas. J. Anim. Sci., 19, pp. 905-908; Morita, H., Kayashita, T., Kobata, H., Gonda, A., Takeya, K., Itokawa, H., Pseudostellarins D-F, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla (1994) Tetrahedron, 50, pp. 9975-9982",
year = "2015",
doi = "10.1021/acs.jafc.5b01026",
language = "English",
volume = "63",
pages = "6181--6188",
journal = "Journal of Agricultural and Food Chemistry",
issn = "0021-8561",
publisher = "American Chemical Society",
number = "27",

}

TY - JOUR

T1 - Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

AU - Tseng, Tien-Sheng

AU - Tsai, Keng-Chang

AU - Chen, Wang-Chuan

AU - Wang, Yeng-Tseng

AU - Lee, Yu-Ching

AU - Lu, Chung-Kuang

AU - Don, Ming-Jaw

AU - Chang, Chang-Yu

AU - Lee, Ching-Hsiao

AU - Lin, Hui-Hsiung

AU - Hsu, Hung-Ju

AU - Hsiao, Nai-Wan

N1 - Export Date: 28 March 2016 CODEN: JAFCA 通訊地址: Hsiao, N.-W.; Institute of Biotechnology, National Changhua University of EducationTaiwan 化學物質/CAS: cysteine, 4371-52-2, 52-89-1, 52-90-4; dopachrome, 3571-34-4; melanin, 8049-97-6; monophenol monooxygenase, 9002-10-2; Cysteine; Dipeptides; dopachrome; Enzyme Inhibitors; Indolequinones; Melanins; Monophenol Monooxygenase 出資詳情: 103-2320-B-077-001-MY3, MOST, Ministry of Science and Technology 出資詳情: MM10211- 0153, MOHW, Ministry of Science and Technology 出資詳情: MM10401-0394, MOHW, Ministry of Science and Technology 參考文獻: Lee, H.E., Kim, E.H., Choi, H.R., Sohn, U.D., Yun, H.Y., Baek, K.J., Kwon, N.S., Kim, D.S., Dipeptides Inhibit Melanin Synthesis in Mel-Ab Cells through Down-Regulation of Tyrosinase (2012) Korean J. Physiol. Pharmacol., 16, pp. 287-291; Brenner, M., Hearing, V.J., The protective role of melanin against UV damage in human skin (2008) Photochem. Photobiol., 84, pp. 539-549; Schallreuter, K., Slominski, A., Pawelek, J.M., Jimbow, K., Gilchrest, B.A., What controls melanogenesis? (1998) Exp. Dermatol., 7, pp. 143-150; Wang, H.M., Chen, C.Y., Wen, Z.H., Identifying melanogenesis inhibitors from Cinnamomum subavenium with in vitro and in vivo screening systems by targeting the human tyrosinase (2011) Exp. Dermatol., 20, pp. 242-248; Lo, C.Y., Liu, P.L., Lin, L.C., Chen, Y.T., Hseu, Y.C., Wen, Z.H., Wang, H.M., Antimelanoma and antityrosinase from Alpinia galangal constituents (2013) Sci. World J., 2013, p. 186505; Iozumi, K., Hoganson, G.E., Pennella, R., Everett, M.A., Fuller, B.B., Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes (1993) J. Invest. Dermatol., 100, pp. 806-811; Chang, T.S., An updated review of tyrosinase inhibitors (2009) Int. J. Mol. Sci., 10, pp. 2440-2475; Seo, S.Y., Sharma, V.K., Sharma, N., Mushroom tyrosinase: Recent prospects (2003) J. Agric. Food Chem., 51, pp. 2837-2853; Passi, S., Nazzaro-Porro, M., Molecular basis of substrate and inhibitory specificity of tyrosinase: Phenolic compounds (1981) Br. J. Dermatol., 104, pp. 659-665; Marusek, C.M., Trobaugh, N.M., Flurkey, W.H., Inlow, J.K., Comparative analysis of polyphenol oxidase from plant and fungal species (2006) J. Inorg. Biochem., 100, pp. 108-123; Katsambas, A.D., Stratigos, A.J., Depigmenting and bleaching agents: Coping with hyperpigmentation (2001) Clin Dermatol, 19, pp. 483-488; Solano, F., Briganti, S., Picardo, M., Ghanem, G., Hypopigmenting agents: An updated review on biological, chemical and clinical aspects (2006) Pigm. Cell Res., 19, pp. 550-571; Asanuma, M., Miyazaki, I., Ogawa, N., Dopamine- or L-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease (2003) Neurotoxic. Res., 5, pp. 165-176; Pan, T., Li, X., Jankovic, J., The association between Parkinson's disease and melanoma (2011) Int. J. Cancer, 128, pp. 2251-2260; Schurink, M., Van Berkel, W.J., Wichers, H.J., Boeriu, C.G., Novel peptides with tyrosinase inhibitory activity (2007) Peptides, 28, pp. 485-495; Arndt, K.A., Fitzpatrick, T.B., Topical use of hydroquinine as a depigmenting agent (1965) J. Am. Med. Assoc., 194, pp. 117-119; Fitzpatrick, T.B., Arndt, K.A., El-Mofty, A.M., Pathak, M.A., Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo (1966) Arch. Dermatol., 93, pp. 589-600; Germanas, J.P., Wang, S., Miner, A., Hao, W., Ready, J.M., Discovery of small-molecule inhibitors of tyrosinase (2007) Bioorg. Med. Chem. Lett., 17, pp. 6871-6875; Ahn, S.M., Rho, H.S., Baek, H.S., Joo, Y.H., Hong, Y.D., Shin, S.S., Park, Y.H., Park, S.N., Inhibitory activity of novel kojic acid derivative containing trolox moiety on melanogenesis (2011) Bioorg. Med. Chem. Lett., 21, pp. 7466-7469; Elsner, P., Maibach, H.I., (2000) Cosmeceuticals: Drugs Vs. Cosmetics, , Eds. CRC Press: Boca Raton, FL, USA; Breathnach, A.C., Nazzaro-Porro, M., Passi, S., Zina, G., Azelaic acid therapy in disorders of pigmentation (1989) Clin. Dermatol, 7, pp. 106-119; Rigoni, C., Toffolo, P., Serri, R., Caputo, R., Use of a cream based on 20% azelaic acid in the treatment of melasma (1989) G. Ital. Dermatol. Venereol., 124, pp. 1-6; Jimbow, K., N -Acetyl-4- S -cysteaminylphenol as a new type of depigmenting agent for the melanoderma of patients with melasma (1991) Arch. Dermatol., 127, pp. 1528-1534; Hamidian, H., Tagizadeh, R., Fozooni, S., Abbasalipour, V., Taheri, A., Namjou, M., Synthesis of novel azo compounds containing 5(4 H)-oxazolone ring as potent tyrosinase inhibitors (2013) Bioorg. Med. Chem., 21, pp. 2088-2092; Hamidian, H., Synthesis of novel compounds as new potent tyrosinase inhibitors (2013) BioMed Res. Int., 2013, p. 207181; Zhu, T.H., Cao, S.W., Yu, Y.Y., Synthesis, characterization and biological evaluation of paeonol thiosemicarbazone analogues as mushroom tyrosinase inhibitors (2013) Int. J. Biol. Macromol., 62, pp. 589-595; Liang, C., Lim, J.H., Kim, S.H., Kim, D.S., Dioscin: A synergistic tyrosinase inhibitor from the roots of Smilax China (2012) Food Chem., 134, pp. 1146-1148; Zheng, Z.P., Tan, H.Y., Wang, M., Tyrosinase inhibition constituents from the roots of Morus australis (2012) Fitoterapia, 83, pp. 1008-1013; Sarkhail, P., Sarkheil, P., Khalighi-Sigaroodi, F., Shafiee, A., Ostad, N., Tyrosinase inhibitor and radical scavenger fractions and isolated compounds from aerial parts of Peucedanum knappii Bornm (2013) Nat. Prod. Res., 27, pp. 896-899; Lee, Y.C., Hsiao, N.W., Tseng, T.S., Chen, W.C., Lin, H.H., Leu, S.J., Yang, E.W., Tsai, K.C., Phage display-mediated discovery of novel tyrosinase-targeting tetrapeptide inhibitors reveals the significance of N-terminal preference of cysteine residues and their functional sulfur atom (2015) Mol. Pharmacol., 87, pp. 218-230; Chen, W.C., Tseng, T.S., Hsiao, N.W., Lin, Y.L., Wen, Z.H., Tsai, C.C., Lee, Y.C., Tsai, K.C., Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling (2015) Sci. Rep., 5, p. 7995; Abu Ubeid, A., Zhao, L., Wang, Y., Hantash, B.M., Short-sequence oligopeptides with inhibitory activity against mushroom and human tyrosinase (2009) J. Invest. Dermatol., 129, pp. 2242-2249; Upadhyay, A., Chompoo, J., Taira, N., Fukuta, M., Gima, S., Tawata, S., Solid-phase synthesis of mimosine tetrapeptides and their inhibitory activities on neuraminidase and tyrosinase (2011) J. Agric. Food Chem., 59, pp. 12858-12863; Noh, J.M., Kwak, S.Y., Kim, D.H., Lee, Y.S., Kojic acid-tripeptide amide as a new tyrosinase inhibitor (2007) Biopolymers, 88, pp. 300-307; Craik, D.J., Fairlie, D.P., Liras, S., Price, D., The future of peptide-based drugs (2013) Chem. Biol. Drug Des., 81, pp. 136-147; Hsiao, N.W., Tseng, T.S., Lee, Y.C., Chen, W.C., Lin, H.H., Chen, Y.R., Wang, Y.T., Tsai, K.C., Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors (2014) J. Chem. Inf. Model., 54, pp. 3099-3111; Takahashi, M., Takara, K., Toyozato, T., Wada, K., A novel bioactive chalcone of Morus australis inhibits tyrosinase activity and melanin biosynthesis in B16 melanoma cells (2012) J. Oleo Sci., 61, pp. 585-592; Kumar, K.J., Yang, J.C., Chu, F.H., Chang, S.T., Wang, S.Y., Lucidone, a novel melanin inhibitor from the fruit of Lindera erythrocarpa Makino (2010) Phytother. Res., 24, pp. 1158-1165; Wang, K.H., Lin, R.D., Hsu, F.L., Huang, Y.H., Chang, H.C., Huang, C.Y., Lee, M.H., Cosmetic applications of selected traditional Chinese herbal medicines (2006) J. Ethnopharmacol., 106, pp. 353-359; Del Marmol, V., Ito, S., Bouchard, B., Libert, A., Wakamatsu, K., Ghanem, G., Solano, F., Cysteine deprivation promotes eumelanogenesis in human melanoma cells (1996) J. Invest. Dermatol., 107, pp. 698-702; McGregor, D., Hydroquinone: An evaluation of the human risks from its carcinogenic and mutagenic properties (2007) Crit. Rev. Toxicol., 37, pp. 887-914; Philips, N., Burchill, D., O'Donoghue, D., Keller, T., Gonzalez, S., Identification of benzene metabolites in dermal fibroblasts as nonphenolic: Regulation of cell viability, apoptosis, lipid peroxidation and expression of matrix metalloproteinase 1 and elastin by benzene metabolites (2004) Skin Pharmacol. Physiol., 17, pp. 147-152; Charlin, R., Barcaui, C.B., Kac, B.K., Soares, D.B., Rabello-Fonseca, R., Azulay-Abulafia, L., Hydroquinone-induced exogenous ochronosis: A report of four cases and usefulness of dermoscopy (2008) Int. J. Dermatol., 47, pp. 19-23; Ito, S., Ojika, M., Yamashita, T., Wakamatsu, K., Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: Implications for melanocyte toxicity (2014) Pigm. Cell Melanoma Res., 27, pp. 744-753; Daquinag, A.C., Sato, T., Koda, H., Takao, T., Fukuda, M., Shimonishi, Y., Tsukamoto, T., A novel endogenous inhibitor of phenoloxidase from Musca domestica has a cystine motif commonly found in snail and spider toxins (1999) Biochemistry, 38, pp. 2179-2188; Kato, N., Sato, S., Yamanaka, A., Yamada, H., Fuwa, N., Nomura, M., Silk protein, sericin, inhibits lipid peroxidation and tyrosinase activity (1998) Biosci., Biotechnol., Biochem., 62, pp. 145-147; Ates, S., Cokmus, C., Partial characterization of a peptide from honey that inhibits mushroom polyphenol oxidase (2001) J. Food Biochem., 25, pp. 127-137; Okot-Kotber, M., Yong, K.J., Bagorogoza, K., Activity and inhibition of polyphenol oxidase in extracts of bran and other milling fractions from a variety of wheat cultivars (2001) Cereal Chem., 78, pp. 514-520; Chen, M.J., Sheu, J.F., Lin, C.W., Chuang, C.L., Study on skin care properties of milk kefir whey (2006) Asian-Australas. J. Anim. Sci., 19, pp. 905-908; Morita, H., Kayashita, T., Kobata, H., Gonda, A., Takeya, K., Itokawa, H., Pseudostellarins D-F, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla (1994) Tetrahedron, 50, pp. 9975-9982

PY - 2015

Y1 - 2015

N2 - Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of melanin cause hyperpigmentation and neurodegenerative diseases. Thus, tyrosinase is promising for use in medicine and cosmetics. Our previous study identified a natural product, A5, resembling the structure of the dipeptide WY and apparently inhibiting tyrosinase. Here, we comprehensively estimated the inhibitory capability of 20 × 20 dipeptides against mushroom tyrosinase. We found that cysteine-containing dipeptides, directly blocking the active site of tyrosinase, are highly potent in inhibition; in particular, N-terminal cysteine-containing dipeptides markedly outperform the C-terminal-containing ones. The cysteine-containing dipeptides, CE, CS, CY, and CW, show comparative bioactivities, and tyrosine-containing dipeptides are substrate-like inhibitors. The dipeptide PD attenuates 16.5% melanin content without any significant cytotoxicity. This study reveals the functional role of cysteine residue positional preference and the selectivity of specific amino acids in cysteine-containing dipeptides against tyrosinase, aiding in developing skin-whitening products. © 2015 American Chemical Society.

AB - Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of melanin cause hyperpigmentation and neurodegenerative diseases. Thus, tyrosinase is promising for use in medicine and cosmetics. Our previous study identified a natural product, A5, resembling the structure of the dipeptide WY and apparently inhibiting tyrosinase. Here, we comprehensively estimated the inhibitory capability of 20 × 20 dipeptides against mushroom tyrosinase. We found that cysteine-containing dipeptides, directly blocking the active site of tyrosinase, are highly potent in inhibition; in particular, N-terminal cysteine-containing dipeptides markedly outperform the C-terminal-containing ones. The cysteine-containing dipeptides, CE, CS, CY, and CW, show comparative bioactivities, and tyrosine-containing dipeptides are substrate-like inhibitors. The dipeptide PD attenuates 16.5% melanin content without any significant cytotoxicity. This study reveals the functional role of cysteine residue positional preference and the selectivity of specific amino acids in cysteine-containing dipeptides against tyrosinase, aiding in developing skin-whitening products. © 2015 American Chemical Society.

KW - dopachrome

KW - eumelanin formation

KW - melanin

KW - molecular docking

KW - peptide

KW - tyrosinase

KW - Amino acids

KW - Melanin

KW - Neurodegenerative diseases

KW - Eumelanins

KW - Hyperpigmentation

KW - Melanin synthesis

KW - Molecular docking

KW - Mushroom tyrosinase

KW - Substrate-like inhibitors

KW - Peptides

KW - Basidiomycota

KW - cysteine

KW - dipeptide

KW - enzyme inhibitor

KW - indole derivative

KW - monophenol monooxygenase

KW - Agaricales

KW - antagonists and inhibitors

KW - biosynthesis

KW - cell line

KW - chemistry

KW - drug screening

KW - enzymology

KW - human

KW - kinetics

KW - melanocyte

KW - metabolism

KW - Cell Line

KW - Cysteine

KW - Dipeptides

KW - Drug Evaluation, Preclinical

KW - Enzyme Inhibitors

KW - Humans

KW - Indolequinones

KW - Kinetics

KW - Melanins

KW - Melanocytes

KW - Molecular Docking Simulation

KW - Monophenol Monooxygenase

U2 - 10.1021/acs.jafc.5b01026

DO - 10.1021/acs.jafc.5b01026

M3 - Article

VL - 63

SP - 6181

EP - 6188

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

SN - 0021-8561

IS - 27

ER -