Monchaud David, Granzhan Anton, Saettel Nicolas, Guédin Aurore, Mergny Jean-Louis, Teulade-Fichou Marie-Paule
Section Recherche, Institut Curie, CNRS UMR176, Centre Universitaire Paris XI, Batiment 110, 91405 Orsay, France.
J Nucleic Acids. 2010 May 24;2010:525862. doi: 10.4061/2010/525862.
Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the "standard" B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes), and in addressing both synthetic issues and biological aspects.
大环支架对于设计选择性G-四链体配体特别有吸引力，主要原因在于，一方面，它们对“标准”B-DNA构象的亲和力较差，另一方面，它们能很好地适配四链体的外部G-四重体。受阳离子卟啉TMPyP4和天然产物端粒抑素的开创性研究的启发，后续研究迅速展开，催生出了具有显著四链体结合特性和生物活性的多种大环结构。在本综述中，我们总结了目前的技术水平，详细阐述了迄今为止所描述的三类主要的四链体结合大环（类端粒抑素多杂芳烃、卟啉及其衍生物、聚铵环番），并探讨了合成问题和生物学方面。
