Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors

Nai Wan Hsiao, Tien Sheng Tseng, Yu Ching Lee, Wang Chuan Chen, Hui Hsiung Lin, Yun Ru Chen, Yeng Tseng Wang, Hung Ju Hsu, Keng Chang Tsai

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Tyrosinase, which is the crucial copper-containing enzyme involved in melanin synthesis, is strongly associated with hyperpigmentation disorders, cancer, and neurodegenerative disease; thus, it has attracted considerable interest in the fields of medicine and cosmetics. The known tyrosinase inhibitors show numerous adverse side effects, and there is a lack of safety regulations governing their use. As a result, there is a need to develop novel inhibitors with no toxicity and long-term stability. In this study, we use molecular docking and pharmacophore modeling to construct a reasonable and reliable pharmacophore model, called Hypo 1, that could be used for identifying potent natural products with crucial complementary functional groups for mushroom tyrosinase inhibition. It was observed that, out of 47 263 natural compounds, A5 structurally resembles a dipeptide (WY) and natural compound B16 is the equivalent of a tripeptide (KFY), revealing that the C-terminus tyrosine residues play a key role in tyrosinase inhibition. Tripeptides RCY and CRY, which show high tyrosinase inhibitory potency, revealed a positional and functional preference for the cysteine residue at the N-terminus of the tripeptides, essentially determining the capacity of tyrosinase inhibition. CRY and RCY used the thiol group of cysteine residues to coordinate with the Cu ions in the active site of tyrosinase and showed reduced tyrosinase activity. We discovered the novel tripeptide CRY that shows the most striking inhibitory potency against mushroom tyrosinase (IC50 = 6.16 μM); this tripeptide is more potent than the known oligopeptides and comparable with kojic acid-tripeptides. Our study provides an insight into the structural and functional roles of key amino acids of tripeptides derived from the natural compound B16, and the results are expected to be useful for the development of tyrosinase inhibitors. (Chemical Equation Presented).

Original languageEnglish
Pages (from-to)3099-3111
Number of pages13
JournalJournal of Chemical Information and Modeling
Volume54
Issue number11
DOIs
Publication statusPublished - 2014 Nov 24

Fingerprint

Neurodegenerative diseases
Melanin
Monophenol Monooxygenase
Cosmetics
Biological Products
Functional groups
Peptides
Medicine
Toxicity
Amino acids
Enzymes
Copper
cosmetics
Acids
Ions
cancer
Group
medicine
Disease
regulation

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

Cite this

Hsiao, Nai Wan ; Tseng, Tien Sheng ; Lee, Yu Ching ; Chen, Wang Chuan ; Lin, Hui Hsiung ; Chen, Yun Ru ; Wang, Yeng Tseng ; Hsu, Hung Ju ; Tsai, Keng Chang. / Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors. In: Journal of Chemical Information and Modeling. 2014 ; Vol. 54, No. 11. pp. 3099-3111.
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abstract = "Tyrosinase, which is the crucial copper-containing enzyme involved in melanin synthesis, is strongly associated with hyperpigmentation disorders, cancer, and neurodegenerative disease; thus, it has attracted considerable interest in the fields of medicine and cosmetics. The known tyrosinase inhibitors show numerous adverse side effects, and there is a lack of safety regulations governing their use. As a result, there is a need to develop novel inhibitors with no toxicity and long-term stability. In this study, we use molecular docking and pharmacophore modeling to construct a reasonable and reliable pharmacophore model, called Hypo 1, that could be used for identifying potent natural products with crucial complementary functional groups for mushroom tyrosinase inhibition. It was observed that, out of 47 263 natural compounds, A5 structurally resembles a dipeptide (WY) and natural compound B16 is the equivalent of a tripeptide (KFY), revealing that the C-terminus tyrosine residues play a key role in tyrosinase inhibition. Tripeptides RCY and CRY, which show high tyrosinase inhibitory potency, revealed a positional and functional preference for the cysteine residue at the N-terminus of the tripeptides, essentially determining the capacity of tyrosinase inhibition. CRY and RCY used the thiol group of cysteine residues to coordinate with the Cu ions in the active site of tyrosinase and showed reduced tyrosinase activity. We discovered the novel tripeptide CRY that shows the most striking inhibitory potency against mushroom tyrosinase (IC50 = 6.16 μM); this tripeptide is more potent than the known oligopeptides and comparable with kojic acid-tripeptides. Our study provides an insight into the structural and functional roles of key amino acids of tripeptides derived from the natural compound B16, and the results are expected to be useful for the development of tyrosinase inhibitors. (Chemical Equation Presented).",
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Hsiao, NW, Tseng, TS, Lee, YC, Chen, WC, Lin, HH, Chen, YR, Wang, YT, Hsu, HJ & Tsai, KC 2014, 'Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors', Journal of Chemical Information and Modeling, vol. 54, no. 11, pp. 3099-3111. https://doi.org/10.1021/ci500370x

Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors. / Hsiao, Nai Wan; Tseng, Tien Sheng; Lee, Yu Ching; Chen, Wang Chuan; Lin, Hui Hsiung; Chen, Yun Ru; Wang, Yeng Tseng; Hsu, Hung Ju; Tsai, Keng Chang.

In: Journal of Chemical Information and Modeling, Vol. 54, No. 11, 24.11.2014, p. 3099-3111.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serendipitous discovery of short peptides from natural products as tyrosinase inhibitors

AU - Hsiao, Nai Wan

AU - Tseng, Tien Sheng

AU - Lee, Yu Ching

AU - Chen, Wang Chuan

AU - Lin, Hui Hsiung

AU - Chen, Yun Ru

AU - Wang, Yeng Tseng

AU - Hsu, Hung Ju

AU - Tsai, Keng Chang

PY - 2014/11/24

Y1 - 2014/11/24

N2 - Tyrosinase, which is the crucial copper-containing enzyme involved in melanin synthesis, is strongly associated with hyperpigmentation disorders, cancer, and neurodegenerative disease; thus, it has attracted considerable interest in the fields of medicine and cosmetics. The known tyrosinase inhibitors show numerous adverse side effects, and there is a lack of safety regulations governing their use. As a result, there is a need to develop novel inhibitors with no toxicity and long-term stability. In this study, we use molecular docking and pharmacophore modeling to construct a reasonable and reliable pharmacophore model, called Hypo 1, that could be used for identifying potent natural products with crucial complementary functional groups for mushroom tyrosinase inhibition. It was observed that, out of 47 263 natural compounds, A5 structurally resembles a dipeptide (WY) and natural compound B16 is the equivalent of a tripeptide (KFY), revealing that the C-terminus tyrosine residues play a key role in tyrosinase inhibition. Tripeptides RCY and CRY, which show high tyrosinase inhibitory potency, revealed a positional and functional preference for the cysteine residue at the N-terminus of the tripeptides, essentially determining the capacity of tyrosinase inhibition. CRY and RCY used the thiol group of cysteine residues to coordinate with the Cu ions in the active site of tyrosinase and showed reduced tyrosinase activity. We discovered the novel tripeptide CRY that shows the most striking inhibitory potency against mushroom tyrosinase (IC50 = 6.16 μM); this tripeptide is more potent than the known oligopeptides and comparable with kojic acid-tripeptides. Our study provides an insight into the structural and functional roles of key amino acids of tripeptides derived from the natural compound B16, and the results are expected to be useful for the development of tyrosinase inhibitors. (Chemical Equation Presented).

AB - Tyrosinase, which is the crucial copper-containing enzyme involved in melanin synthesis, is strongly associated with hyperpigmentation disorders, cancer, and neurodegenerative disease; thus, it has attracted considerable interest in the fields of medicine and cosmetics. The known tyrosinase inhibitors show numerous adverse side effects, and there is a lack of safety regulations governing their use. As a result, there is a need to develop novel inhibitors with no toxicity and long-term stability. In this study, we use molecular docking and pharmacophore modeling to construct a reasonable and reliable pharmacophore model, called Hypo 1, that could be used for identifying potent natural products with crucial complementary functional groups for mushroom tyrosinase inhibition. It was observed that, out of 47 263 natural compounds, A5 structurally resembles a dipeptide (WY) and natural compound B16 is the equivalent of a tripeptide (KFY), revealing that the C-terminus tyrosine residues play a key role in tyrosinase inhibition. Tripeptides RCY and CRY, which show high tyrosinase inhibitory potency, revealed a positional and functional preference for the cysteine residue at the N-terminus of the tripeptides, essentially determining the capacity of tyrosinase inhibition. CRY and RCY used the thiol group of cysteine residues to coordinate with the Cu ions in the active site of tyrosinase and showed reduced tyrosinase activity. We discovered the novel tripeptide CRY that shows the most striking inhibitory potency against mushroom tyrosinase (IC50 = 6.16 μM); this tripeptide is more potent than the known oligopeptides and comparable with kojic acid-tripeptides. Our study provides an insight into the structural and functional roles of key amino acids of tripeptides derived from the natural compound B16, and the results are expected to be useful for the development of tyrosinase inhibitors. (Chemical Equation Presented).

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