Synthesis and Biological Evaluation of Ascorbyl-Conjugated Peptide Derivatives as Collagen Synthesis Stimulating Agents in Human Skin Fibroblasts

Vitamin C (ascorbic acid) is a widely used agent for anti-aging and whitening in the field of cosmetics. It affects collagen production in skin cells, inhibits melanin synthesis, displays anti-oxidant activity, and improves the immune system. However, vitamin C has limitations in cell permeability and environmental condition such as heating and lighting decrease its stability. Thus, vitamin C derivatives are being developed to overcome these problems. In this study, we synthesized vitamin C derivatives with a succinoyl group at the 2-position and peptides in the form of ester bonds. We then evaluated the cytotoxicity and collagen synthesis activity of these new compounds in human skin fibroblasts. Vitamin C-conjugated peptides were also synthesized in ether and carbamate forms, and the optimal combination conditions of vitamin C and peptides were identified. In addition, collagen synthesis-stimulating activity of vitamin C-conjugated peptides was also evaluated and compared to the effects of vitamin C alone. Based on these results, we confirmed that the ester-bonded vitamin C-conjugated peptide GEKG showed more stimulating effect on the production of collagen and related gene expression than either vitamin C or GEKG alone. This study will provide important information for developing skin health products and other topical cosmetics using vitamin C and peptides.