Novotný Jan, Yurenko Yevgen P, Kulhánek Petr, Marek Radek
CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5/A4, Brno, CZ-625 00, Czech Republic.
Phys Chem Chem Phys. 2014 Aug 7;16(29):15241-8. doi: 10.1039/c4cp00541d.
Guanine DNA quadruplexes are interesting and important biological objects because they represent potential targets for regulatory drugs. Their use as building blocks for biomaterial applications is also being investigated. This contribution reports the in silico design of artificial building blocks derived from xanthine. Methods of quantum chemistry were used to evaluate the properties of xanthine structures relative to those containing guanine, the natural reference used. Tailoring the xanthine core showed that the base stacking and the ion coordination were significantly enhanced in the designed systems, while the ion-transport properties were not affected. Our study suggests that the 9-deaza-8-haloxanthine bases (where the halogen is fluorine or chlorine) are highly promising candidates for the development of artificial quadruplexes and quadruplex-active ligands.
鸟嘌呤DNA四链体是有趣且重要的生物对象，因为它们是调节药物的潜在靶点。它们作为生物材料应用构建块的用途也正在研究中。本文报道了源自黄嘌呤的人工构建块的计算机辅助设计。采用量子化学方法评估了黄嘌呤结构相对于含鸟嘌呤的天然参考结构的性质。对黄嘌呤核心进行定制表明，在设计的体系中碱基堆积和离子配位显著增强，而离子传输性质不受影响。我们的研究表明，9-脱氮-8-卤代黄嘌呤碱基（其中卤素为氟或氯）是开发人工四链体和四链体活性配体的极具潜力的候选物。
