左旋多巴酪氨酰酪氨酸二肽的合成及与DNA的相互作用

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

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.

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 absorp- tion 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 inter- calation binding. Compared with L-dopa, the interaction between L-dopa-L-Tyr-L-Tyr and DNA was stronger.