Department of Chemical Engineering , Hanyang University , Ansan 426-791 , Republic of Korea.
School of Chemical and Biological Engineering , Seoul National University , Seoul 151-744 , Republic of Korea.
Bioconjug Chem. 2018 Apr 18;29(4):1000-1005. doi: 10.1021/acs.bioconjchem.8b00050. Epub 2018 Mar 15.
The regulation of tyrosinase activity and reactive oxygen species is of great importance for the prevention of dermatological disorders in the fields of medicine and cosmetics. Herein, we report a strategy based on solid-phase peptide chemistry for the synthesis of β-lactoglobulin peptide fragment/caffeic acid (CA) conjugates (CA-Peps) with dual activities of tyrosinase inhibition and antioxidation. The purity of the prepared conjugates, CA-MHIR, CA-HIRL, and CA-HIR, significantly increased to 99%, as acetonide-protected CA was employed in solid-phase coupling reactions on Rink amide resins. The tyrosinase inhibitory activities of all CA-Pep derivatives were higher than the activity of kojic acid, and CA-MHIR exhibited the highest tyrosinase inhibition activity (IC = 47.9 μM). Moreover, CA-Pep derivatives displayed significantly enhanced antioxidant activities in the peroxidation of linoleic acid as compared to the pristine peptide fragments. All CA-Pep derivatives showed no cytotoxicity against B16-F1 melanoma cells.
酪氨酸酶活性和活性氧的调节对于医学和化妆品领域预防皮肤疾病至关重要。在此，我们报告了一种基于固相肽化学的策略，用于合成具有双重酪氨酸酶抑制和抗氧化活性的β-乳球蛋白肽片段/咖啡酸（CA）缀合物（CA-Peps）。在 Rink 酰胺树脂上的固相偶联反应中使用了乙酰保护的 CA，使制备的缀合物 CA-MHIR、CA-HIRL 和 CA-HIR 的纯度显著提高到 99%。所有 CA-Pep 衍生物的酪氨酸酶抑制活性均高于曲酸的活性，CA-MHIR 表现出最高的酪氨酸酶抑制活性（IC = 47.9 μM）。此外，与原始肽片段相比，CA-Pep 衍生物在亚油酸过氧化中表现出显著增强的抗氧化活性。所有 CA-Pep 衍生物对 B16-F1 黑色素瘤细胞均无细胞毒性。
