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Aiming to improve binding of porphyrin diphenyl guanidinium conjugates to guanine-quadruplexes: When size matters
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2022-08-27 , DOI: 10.1016/j.bmcl.2022.128954
Nikolina Stipaničev 1 , Konstantin Raabe 1 , Isabel Rozas 1
Affiliation  

Aiming to improve the binding to Guanine quadruplexes of different topologies, docking studies of porphyrin diphenyl guanidine conjugates previously prepared with an O or a S bridge between the diphenyl moiety and a newly design derivative with an SO2 bridge were carried out using different guanine quadruplexes of different topologies (four parallel, one antiparallel and one hybrid). Positive results were obtained from these computational studies drove us to prepare the SO2 bridge conjugate improving the synthetic route previously reported by us. Biophysical experiments such as UV-thermal melting and circular dichroism indicated the lack of binding to the double stranded DNA and poor binding of the new derivative prepared to any of the guanine quadruplexes studied. These results show that the size of this SO2 bridge could be responsible of the poor experimental binding to guanine quadruplexes.



中文翻译:

旨在改善卟啉二苯基胍鎓缀合物与鸟嘌呤-四链体的结合:当大小很重要时

为了改善与不同拓扑结构的鸟嘌呤四链体的结合,使用不同的鸟嘌呤四链体对先前在二苯基部分之间用 O 或 S 桥制备的卟啉二苯基胍缀合物与具有 SO 2桥的新设计衍生物进行对接研究。不同的拓扑结构(四个并行,一个反并行和一个混合)。从这些计算研究中获得了积极的结果,促使我们制备 SO 2桥共轭改进了我们之前报道的合成路线。紫外热熔解和圆二色性等生物物理实验表明与双链 DNA 缺乏结合,并且制备的新衍生物与所研究的任何鸟嘌呤四链体的结合较差。这些结果表明,这种 SO 2桥的大小可能是实验与鸟嘌呤四链体结合不良的原因。

更新日期:2022-08-31
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