Synthesis of lipoic acid–peptide conjugates and their effect on collagen and melanogenesis

• LA–peptide conjugates were prepared by linking lipoic acid to the pentapeptide KTTKS.
• Conjugates showed the inhibitory effect on melanin synthesis and tyrosinase activity.
• Conjugates inhibit UV-induced matrix metalloproteinase-1 expression.
• Conjugates stimulate collagen biosynthesis in fibroblasts.
• Conjugates showed a dual anti-melanogenic and anti-aging effect.

We report new examples of lipoic acid (LA)–peptide conjugates, their potential as codrugs having anti-melanogenic and anti-aging properties was evaluated. These multifunctional molecules were prepared by linking lipophilic moiety (LA) to the pentapeptide KTTKS. The inhibitory effect of LA–peptide conjugates on melanin synthesis and tyrosinase activity is stronger than that of LA or the pentapeptide alone. Importantly, the conjugates display no cytotoxicity at a high concentration. LA–KTTKS and LA–PEG–KTTKS also inhibit UV-induced matrix metalloproteinase-1 expression up to 49.5% and 69.5% at 0.5 mM, respectively. LA–peptide conjugates stimulate collagen biosynthesis in fibroblasts more efficiently than their parent molecules do. These data suggest that LA–peptide conjugates may have cosmeceutical application as anti-melanogenic and anti-aging agents.

The multifunctional conjugates, obtained by joining α-lipoic acid (LA) with pentapeptide KTTKS, were designed and synthesized as potential bifunctional agents combining anti-melanogenic and anti-aging properties.Figure optionsDownload as PowerPoint slide