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.

Original languageEnglish
Pages (from-to)6181-6188
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume63
Issue number27
DOIs
Publication statusPublished - 2015 Jul 15

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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

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

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.
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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.",
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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, 15.07.2015, p. 6181-6188.

Research output: Contribution to journalArticle

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T1 - Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase

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AU - Tseng, Tien Sheng

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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

PY - 2015/7/15

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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.

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.

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