Takeuchi Ryusuke, Zou Tingting, Wakahara Daiki, Nakano Yoshifumi, Sato Shinobu, Takenaka Shigeori
Department of Applied Chemistry, Kyushu Institute of Technology, Fukuoka, 804-8550, Japan.
Research Center for Bio-microsensing Technology, Kyushu Institute of Technology, Fukuoka, 804-8550, Japan.
Chemistry. 2019 Jul 2;25(37):8691-8695. doi: 10.1002/chem.201901468. Epub 2019 May 27.
A new type of dimeric cyclic naphthalene diimide derivatives (cNDI-dimers) carrying varied linker length were designed and synthesized to recognize dimeric G-quadruplex structures. All of the cNDI-dimers exhibited a high preference for recognizing G-quadruplex structures, and significantly enhanced the thermal stability of the dimeric G-quadruplex structure over the cNDI monomer by increasing the melting temperature by more than 23 °C, which indicated the strengthened ability of cNDI dimers for stabilizing dimeric G-quadruplex. cNDI dimers also showed a stronger ability to inhibit telomerase activity and stop telomere DNA elongation than cNDI monomer, which showed an improved anticancer potentiality for further therapeutic application.
设计并合成了一类新型的带有不同连接子长度的二聚体环状萘二亚胺衍生物(cNDI-二聚体),用于识别二聚体G-四链体结构。所有的cNDI-二聚体在识别G-四链体结构方面表现出高度偏好性,并且通过使熔解温度提高超过23 °C,显著增强了二聚体G-四链体结构相对于cNDI单体的热稳定性,这表明cNDI二聚体稳定二聚体G-四链体的能力增强。与cNDI单体相比,cNDI二聚体还表现出更强的抑制端粒酶活性和阻止端粒DNA延伸的能力,这显示出其在进一步治疗应用中具有更好的抗癌潜力。