Park Yong-Doo, Lyou You-Jeong, Hahn Hwa-Sun, Hahn Myong-Joon, Yang Jun-Mo
Department of Dermatology, Sungkyunkwan University
J Biomol Struct Dyn. 2006 Oct;24(2):131-8. doi: 10.1080/07391102.2006.10507106.
The inhibition of tyrosinase has attracted considerable attention for potential medicinal and cosmetic applications, as well as in agriculture. This study investigated the inhibition effects of thiol-associated Cu(2+) chelators and deduced a strategy for designing and/or selecting tyrosinase inhibitors. Among the several compounds tested, dithioglycerine (DTGC) was selected for further experiments on the inhibition kinetics on tyrosinase. Different types of tyrosinases derived from mushroom and from the transient overexpression in HEK293 cells were tested individually. The results showed that DTGC significantly inhibited human tyrosinase in a complex manner (slope-parabolic mixed-type inhibition), which was comparable to mushroom tyrosinase. The affinity of DTGC affinity to human tyrosinase was evaluated by setting up a K(i slope) equation. The results suggest that a Cu(2+) chelator modified with thiol groups has potential as a whitening agent. In addition, a strategy for designing and/or selecting tyrosinase inhibitors that target the active enzyme site was also suggested.
酪氨酸酶的抑制作用在潜在的医学、化妆品应用以及农业领域都引起了相当大的关注。本研究调查了硫醇相关的Cu(2+)螯合剂的抑制作用，并推导了一种设计和/或选择酪氨酸酶抑制剂的策略。在所测试的几种化合物中，选择了二硫代甘油（DTGC）对酪氨酸酶的抑制动力学进行进一步实验。分别测试了来自蘑菇和在HEK293细胞中瞬时过表达的不同类型的酪氨酸酶。结果表明，DTGC以复杂的方式（斜率-抛物线混合型抑制）显著抑制人酪氨酸酶，这与蘑菇酪氨酸酶相当。通过建立K(i斜率)方程评估了DTGC对人酪氨酸酶的亲和力。结果表明，用硫醇基团修饰的Cu(2+)螯合剂有作为美白剂的潜力。此外，还提出了一种设计和/或选择靶向活性酶位点的酪氨酸酶抑制剂的策略。
