title: A Novel Heptapeptide with Tyrosinase Inhibitory Activity Identified from a Phage Display Library.
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 IC50values 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.
authors.affiliation: Key Laboratory of Textile Science & Technology, Ministry of Education, Donghua University, Shanghai, 201620, People's Republic of China. niehuali@dhu.edu.cn.|College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China. niehuali@dhu.edu.cn.
authors.forename: Huali
authors.initials: H
authors.lastname: Nie
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Hongzhen
authors.initials: H
authors.lastname: Guo
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Yuanhao
authors.initials: Y
authors.lastname: Tan
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Quan
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People's Republic of China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000363:Agaricales / Q000737:chemistry; D002384:Catalysis; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007700:Kinetics; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019151:Peptide Library; D010455:Peptides; D010088:Oxidoreductases; C412191:monophenolase; D014442:Monophenol Monooxygenase
keywords: Heptapeptide; Inhibition; Molecular docking; Mushroom tyrosinase; Phage display