The C‐terminally shortened analogs of a hexapeptide derived from Lingzhi hydrolysate with enhanced tyrosinase‐inhibitory activity

Abstract Ganoderma lucidum or Lingzhi (Chinese) is a medicinal fungus widely used in traditional medicine as a health supplement. This study was conducted to identify an approach to enhance the anti‐tyrosinase activity of a peptide from G. lucidum by chemical modification of its C‐terminus. The original peptide was obtained from protease‐digested Lingzhi proteins, followed by ultrafiltration (molecular weight cut‐off 3 kDa) and C18 solid‐phase extraction. The hexapeptide (NH 2 –VLTCGF–COOH) possessing the anti‐tyrosinase activity was identified by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). This hexapeptide was subjected to shortening to enhance the anti‐tyrosinase activity. Both the original peptide and the shortened peptides were synthesized by solid‐phase peptide synthesis. The purity and mass of the synthetic peptide and the modified peptide were evaluated by high‐performance liquid chromatography and LC‐MS, respectively. Comparison of the tyrosinase activities showed that the modified peptide demonstrated more than 23.27 ± 1.07% activity, which was better than that of the hexapeptide. The structure‐related biological activity was explained by molecular docking, wherein the VLT–tyrosinase complex showed two interaction forces: Asn260 and Gly281 through H‐bonding and Glu256 through electrostatic interaction. This information could help toward gaining further understanding of the correlation between the anti‐tyrosinase activity and the molecular structure of the modified hexapeptide and support its potential use as a safe cosmetic ingredient with tyrosinase‐suppressing ability.