Guanine‐rich nucleic acid sequences able to form four‐stranded structures (G‐quadruplexes, G4) play key cellular regulatory roles and are considered as promising drug targets for anticancer therapy. On the basis of the organization of their structural elements, G4 ligands can be divided into three major families: one, fused heteroaromatic polycyclic systems; two, macrocycles; three, modular aromatic compounds. The design of modular G4 ligands emerged as the answer to achieve not only more drug‐like compounds but also more selective ligands by targeting the diversity of the G4 loops and grooves. The rationale behind the design of a very comprehensive set of ligands, with particular focus on the structural features required for binding to G4, is discussed and combined with the corresponding biochemical/biological data to highlight key structure–G4 interaction relationships. Analysis of the data suggests that the shape of the ligand is the major factor behind the G4 stabilizing effect of the ligands. The information here critically reviewed will certainly contribute to the development of new and better G4 ligands with application either as therapeutics or probes.

中文翻译：

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模块化G四元配体的设计

能够形成四链结构的富含鸟嘌呤的核酸序列（G-四链体，G4）起关键的细胞调节作用，被认为是抗癌治疗的有希望的药物靶标。根据其结构元素的组织，G4配体可分为三个主要家族：一是稠合的杂芳族多环系统；一是稠合的多环多环系统。二，大周期；三，模块化的芳香族化合物。通过针对G4环和凹槽的多样性，模块化G4配体的设计应运而生，不仅可以实现更多的类药物化合物，而且可以实现更具选择性的配体。设计非常全面的配体的基本原理，特别是结合G4所需的结构特征，讨论并与相应的生化/生物学数据结合以突出显示关键结构–G4相互作用关系。数据分析表明，配体的形状是配体G4稳定作用背后的主要因素。经过严格审查的信息必将有助于开发新的更好的G4配体，并将其用作治疗剂或探针。