四取代咪唑的合成及与G-四链体相互作用研究

Study the synthesis of tetra-substituted imidazole and the interaction with G-quadruplexs

目的合成四取代咪唑5a,并研究其与G-四链体的相互作用。方法以2,2-双(4-甲基哌嗪基苯基)乙二酮为原料,合成得到了化合物5a。采用紫外光谱实验和荧光光谱实验评价5a与G-四链体的相互作用,采用DNA荧光共振能量转移(FRET-melting)实验、CD实验、分子对接分析研究5a与G-四连体DNA的相互作用模式和机制。结果荧光光谱实验结果表明5a对部分正平行型G-四链体,尤其是c-myc G-四链体,具有一定的荧光识别作用。FRETmelting实验结果表明5a对c-myc G-四链体具有较好的稳定作用,CD实验和分子对接分析结果表明5a能维持cmyc G-四链体的正平行型构象,与c-myc G-四链体发生π-π堆积作用和静电吸引作用,导致5a的分子构象发生变化,从而发射出荧光。结论5a对c-myc G-四链体具有一定的荧光响应,为新型靶向识别c-myc G-四链体探针的发现提供了研究基础。

Objective To synthetize tetra-substituted imidazole 5a and study the interaction with G-quadruplexs.Methods Compound 5a was synthesized by using 2,2-bis(4-methylpiperazinylphenyl)ethylenedione as a starting material.The interaction between 5A and G-quadruplex was evaluated by UV and fluorescence spectroscopy.The interaction mode and mechanism between 5A and G-quadruplex DNA were studied by DNA FRET-melting assay,CD assay and molecular docking analysis.Results The results of fluorescence spectroscopy revealed that 5a had certain fluorescence recognition on most parallel G-quadruplexs,especially c-myc G-quadruplex.The results of FRET-melting assay showed 5a could stabilize c-myc G-quadruplex.The results of CD assay and molecular docking analysis revealed that 5a could maintain parallel type conformation of c-myc G-quadruplex.5a could effectively possessπ-πstacking interactions and electrostatic interactions with c-myc G-quadruplex,which resulted in a change in the conformation of the 5a molecule to emit fluorescence.Conclusion 5a has certain fluorescence response on c-myc G-quadruplex,which provides a research basis for the discovery of novel targeted recognition probes to c-myc G-quadruplex.