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

Synthesis and DNA Binding Properties of Terpyridine-naphthalimide Conjugates

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CT DNA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NPI1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 absorptionspectroscopy, circular dichroism （CD） spectroscopy and fluorescence resonance energy transfer （FRET） assay. NPI1 and NPI2 possess high affinity to G-quadruplex and resonable selectivity over duconstant between NPI2 and G-quadruplex is 1. 06×108 L/mol in buffer solution containing fold as that between NPI2 and CT DNA. Circular dichroism results suggest that in theHtelo 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 stacking, electrostaticinteraction and hydrogen bonding, resulting in the high affinity of these compounds to G-quadruplex （Ka〉 107L/mol）.