Kojic acid-tripeptide amide as a new tyrosinase inhibitor

Twenty two kojic acid-tripeptide amides were prepared using a solid-phase Fmoc/tBu strategy with Rink Amide SURk (R) resin. To effectively obtain kojic acid-tripeptide amide conjugates, the coupling conditions of kojic acid to the tripeptide on the resin were optimized. The tyrosinase inhibitory activity of kojic acid-tripeptide amides and the effect of the amino acid sequence on the activity were compared with those of kojic acid-tripeptide acids. The stability of kojic acid-tripeptide amides were then compared with those of kcjic acid and kojic acid-tripeptides acids. As a consequence, kojic acid-FWY-NH2 proved to be the best compound, with the highest inhibitory activity, which was maintained over different storage times tinder various temperatures and pHs. (c) 2007 Wiley Periodicals, Inc.