Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy.
Molecules. 2022 Jun 29;27(13):4165. doi: 10.3390/molecules27134165.
G-quadruplexes (G4) are now extensively recognised as a peculiar non-canonical DNA geometry that plays a prime importance role in processes of biological relevance whose number is increasing continuously. The same is true for the less-studied RNA G4 counterpart. G4s are stable structures; however, their geometrical parameters may be finely tuned not only by the presence of particular sequences of nucleotides but also by the salt content of the medium or by a small molecule that may act as a peculiar topology inducer. As far as the interest in G4s increases and our knowledge of these species deepens, researchers do not only verify the G4s binding by small molecules and the subsequent G4 stabilisation. The most innovative studies now aim to elucidate the mechanistic details of the interaction and the ability of a target species (drug) to bind only to a peculiar G4 geometry. In this focused review, we survey the advances in the studies of the binding of small molecules of medical interest to G4s, with particular attention to the ability of these species to bind differently (intercalation, lateral binding or sitting atop) to different G4 topologies (parallel, anti-parallel or hybrid structures). Some species, given the very high affinity with some peculiar G4 topology, can first bind to a less favourable geometry and then induce its conversion. This aspect is also considered.
四链体（G4）现在被广泛认为是一种特殊的非经典 DNA 构象，在不断增加的生物学相关过程中起着重要作用。研究较少的 RNA G4 对应物也是如此。G4 是稳定的结构；然而，它们的几何参数不仅可以通过特定核苷酸序列的存在来精细调节，还可以通过介质中的盐含量或可能作为特殊拓扑诱导剂的小分子来调节。随着人们对 G4 的兴趣不断增加，我们对这些物质的了解也不断加深，研究人员不仅验证了小分子与 G4 的结合以及随后 G4 的稳定化。现在最具创新性的研究旨在阐明相互作用的机制细节以及目标物种（药物）仅与特定 G4 几何形状结合的能力。在本次重点综述中，我们调查了具有医学意义的小分子与 G4 结合的研究进展，特别关注这些物质结合不同（嵌入、侧向结合或位于顶部）不同 G4 拓扑结构（平行、反平行或混合结构）的能力。有些物质由于与某些特殊的 G4 拓扑结构具有非常高的亲和力，因此可以首先与不太有利的几何形状结合，然后诱导其转化。这一方面也被考虑在内。
