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A Novel Heptapeptide with Tyrosinase Inhibitory Activity Identified from a Phage Display Library

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Abstract

Peptidic inhibition of the enzyme tyrosinase, responsible for skin pigmentation and food browning, would be extremely useful for the food, cosmetics, and pharmaceutical industries. In order to identify novel inhibitory peptides, a library of short sequence oligopeptides was screened to reveal direct interaction with the tyrosinase. A phage displaying heptapeptide (IQSPHFF) was found to bind most strongly to tyrosinase. The inhibitory activity of the heptapeptide was evaluated using mushroom tyrosinase. The results showed that the peptide inhibited both the monophenolase and diphenolase activities of mushroom tyrosinase with IC50 values of 1.7 and 4.0 mM, respectively. The heptapeptide is thought to be a reversible competitive inhibitor of diphenolase with the inhibition constants (Ki) of 0.765 mM. To further investigate how the heptapeptide exerts its inhibitory effect, a docking study between tyrosinase and heptapeptide was performed. The simulation showed that the heptapeptide binds in the active site of the enzyme near the catalytically active Cu ions and forms hydrogen bonds with five histidine residues on the active site. Phage display technology is thus a useful approach for the screening of potential tyrosinase inhibitors and could be widely applicable to a much wider range of enzymes.

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Acknowledgments

This work was financially supported by the Shanghai Natural Science Foundation (14ZR1401300), the Shanghai Pujiang Program (16PJD007) and the Fundamental Research Funds for the Central Universities (2232015D3-15).

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Authors and Affiliations

  1. Key Laboratory of Textile Science & Technology, Ministry of Education, Donghua University, Shanghai, 201620, People’s Republic of China

    Huali Nie

  2. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People’s Republic of China

    Huali Nie, Lin Liu, Huiqin Yang, Hongzhen Guo, Xiang Liu, Yuanhao Tan, Wen Wang, Jing Quan & Limin Zhu

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  1. Huali Nie
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  2. Lin Liu
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  3. Huiqin Yang
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  7. Wen Wang
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  9. Limin Zhu
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Correspondence to Huali Nie.

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Highlights

• A novel heptapeptide with tyrosinase inhibitory activity was identified.

• A phage display technology was used in screening an enzyme inhibitor.

• A docking study between tyrosinase and heptapeptide was performed.

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Nie, H., Liu, L., Yang, H. et al. A Novel Heptapeptide with Tyrosinase Inhibitory Activity Identified from a Phage Display Library. Appl Biochem Biotechnol 181, 219–232 (2017). https://doi.org/10.1007/s12010-016-2208-3

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  • DOI: https://doi.org/10.1007/s12010-016-2208-3

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