三联吡啶-萘酰亚胺二元化合物的合成及其与DNA的相互作用

摘要

本文合成了两种三联吡啶修饰的萘酰亚胺化合物NPI1和NPI2,并利用紫外-可见吸收光谱(UV-Vis)、圆二色光谱(CD)、荧光共振能量转移(FRET)等方法研究了它们与双链CTDNA和Htelo G-四链体DNA的相互作用.实验结果表明,化合物NPI1和NPI2对G四链体DNA具有很好的结合能力和选择性,溶液中的碱金属离子种类和萘酰亚胺基团上的取代基对NPII和NPI2与DNA的作用有很大的影响.在含K+的缓冲液中,NPI2与G-四链体的结合常数达到1.06×108 L/mol,是与双链CT DNA结合常数的268倍.圆二色谱结果表明在不含碱金属离子的溶液中,NPI1和NPI2可诱导Htelo DNA形成反平行结构G-四链体.Autodock分子对接模拟表明NPI1和NPI2可以通过堆积作用、静电作用、氢键等作用方式与G-四链体结合,使得它们对G-四链体具有很高亲和性(Ka＞ 107 L/mol).%Two terpyridine-naphthalimide conjugates NPI1 and NPI2 are synthesized,and their interaction with duplexcalf thymus DNA (CT DNA) and Htelo G-quadruplex DNA are investigated by UV-Vis absorption spectroscopy,circular dichroism (CD) spectroscopy and fluorescence resonance energy transfer (FRET) assay.NPI1 and NPI2 possess high affinity to G-quadruplex and resonable selectivity over duplex.The association constant between NPI2 and G-quadruplex is 1.06 × 108 L/mol in buffer solution containing K+,which is 268-fold as that between NPI2 and CT DNA.Circular dichroism results suggest that in the absence of K+,the Htelo DNA can form anti-parallel structure of G-quadruplex upon addition of NPI1 and NPI2.Molecular docking studies indicate that NPI1 and NPI2 interact with telomeric G-quadruplex through π-π stacking,electrostatic interaction and hydrogen bonding,resulting in the high affinity of these compounds to G-quadruplex (Ka＞107 L/mol).