Tyrosinase inhibitory peptides: Structure-activity relationship study on peptide chemical properties, terminal preferences and intracellular regulation of melanogenesis signaling pathways

Bioactive peptides have gained attention as potential alternatives to chemical-based skin lightening agents. Based on literature search, the reported articles focused mainly on the sources and preparation methods of tyrosinase inhibitory peptides and there is lacking information regarding the structure-activity relationship (SAR) between peptide property and tyrosinase inhibition. It was hypothesized that peptide properties such as hydrophobicity/hydrophilicity and the amino acid type and position/arrangement at the terminal positions could affect peptide mode of binding hence result in various degrees of tyrosinase inhibition.In this study, the sequences of 128 tyrosinase inhibitory peptides were collected from peer-reviewed articles. The hydrophobicity/hydrophilicity property and the amino acid profile of peptides at the N- and C-terminals were analyzed using bioinformatics tools. Molecular docking analysis was employed to further elucidate the roles of reactive amino acids in tyrosinase-peptide binding interactions. The peptide-regulated intracellular melanogenesis pathways were also compiled and discussed.It was found that hydrophobic and/or polar neutral properties may facilitate or stabilize peptide binding with tyrosinase. Moreover, short peptides featuring a cysteine and tyrosine at the N- and C- terminal ultimate positions tend to bind to the active site of tyrosinase whereas positively charged amino acid such as arginine at the N-terminal does not favor peptide binding to tyrosinase.These findings provide detailed explanation on how peptide/amino acid structures are related and what function they play in tyrosinase inhibition. It could also inspire researchers to account for tyrosinase-peptide SAR and the underlying anti-melanogenesis mechanisms in formulating peptide-based treatments or strategies against skin hyperpigmentation.