左旋多巴酪氨酰酪氨酸二肽的合成及与DNA的相互作用

采用Fmoc固相法合成了左旋多巴酪氨酰酪氨酸二肽(L-dopa-L-Tyr-L-Tyr), 并经RP-HPLC分离和纯化, 通过ESI-MS,¹H NMR和¹³C NMR表征了其结构. 采用紫外光谱、荧光光谱和琼脂糖凝胶电泳研究了左旋多巴(L-dopa)及L-dopa-L-Tyr-L-Tyr与DNA的相互作用. 结果表明, 随着L-dopa和L-dopa-L-Tyr-L-Tyr浓度的增加, 体系的紫外光谱呈减色效应; 根据Stern-Volmer方程可知荧光猝灭方式为静态猝灭; 琼脂糖凝胶电泳中, pUC18DNA的迁移速率变慢. 推测L-dopa和L-dopa-L-Tyr-L-Tyr与ctDNA作用模式为嵌入作用. 与L-dopa相比, L-dopa-L-Tyr-L-Tyr与DNA的相互作用更强.

Synthesis and Interaction of L-dopa-L-Tyr-L-Tyr with DNA

In order to improve the bioavailability of levodopa drug, reduing DNA damage, L-dopa-L-Tyr-L-Tyr was synthesized by Fmoc solid-phase synthesis, which was separated and purified by reversed-phase HPLC, and the product was characterized via ESI-MS,¹H NMR and ¹³C NMR. The interactions of L-dopa and L-dopa-L-Tyr-L-Tyr with ctDNA were investigated by ultraviolet, fluorescence spectra and agarose gel electrophoresis. The results showed that remarkable hypochromic effect was observed on the ultraviolet absorption spectra and the fluorescence quenching mechanism was static quenching by Stern-Volmer equation. The migration rate of pUC18 DNA became slow on the agarose gel electrophoresis, in the presence of increasing amounts of L-dopa and L-dopa-L-Tyr-L-Tyr. L-dopa and L-dopa-L-Tyr-L-Tyr might interact with DNA by intercalation binding. Compared with L-dopa, the interaction between L-dopa-L-Tyr-L-Tyr and DNA was stronger.