Pearl peptides (Hyriopsis Cumingii) as tyrosinase inhibitors: identification, characterization, inhibitory activity, conformational change and mechanism

Pearl protein extracted from freshwater mussels has been shown to inhibit tyrosinase activity. However, the unclear inhibitory mechanism and associated conformational changes limit their practical applications. In this study, peptides from the crude extract of pearl powder are analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). These peptides are subsequently assessed for their tyrosinase inhibitory potential via molecular docking techniques. Notably, experiments reveal that a small-molecule peptide effectively prevents the interaction between 3,4-dihydroxyphenylalanine (L-DOPA) and tyrosinase, impeding the formation of dopaquinone. The peptide GLGGGLAGAGGADGA (95P, 1099.54 Da) shows particular promise, with synthesized 95P inhibiting both the monophenolase and diphenolase activities of tyrosinase, with IC ₅₀ values of 30.97 ± 0.75 μM and 64.62 ± 3.08 μM,respectively. 95P inhibits tyrosinase activity in a mixed competitive and reversible manner. Molecular dynamics simulations suggest that 95P stabilizes 5M8N, impeding structural contraction identified by model number 5M8N. In conclusion, 95P is a powerful and stable tyrosinase inhibitor with the potential to be used as a skin whitening agent in the pharmaceutical field and an anti-browning agent in the food industry.