The development of innovative methodologies to identify RNA binders has attracted enormous attention in chemical biology and drug discovery. Although antibiotics targeting bacterial ribosomal RNA have been on the market for decades, the renewed interest in RNA targeting reflects the need to better understand complex intracellular processes involving RNA. In this context, small molecules are privileged tools used to explore the biological functions of RNA and to validate RNAs as therapeutic targets, and they eventually are to become new drugs. Despite recent progress, the rational design of specific RNA binders requires a better understanding of the interactions which occur with the RNA target to reach the desired biological response. In this Review, we discuss the challenges to approaching this underexplored chemical space, together with recent strategies to bind, interact and affect biologically relevant RNAs.

识别 RNA 结合剂的创新方法的发展引起了化学生物学和药物发现领域的极大关注。尽管针对细菌核糖体 RNA 的抗生素已上市数十年，但人们对 RNA 靶向的新兴趣反映出需要更好地了解涉及 RNA 的复杂细胞内过程。在这种背景下，小分子是用于探索 RNA 生物学功能并验证 RNA 作为治疗靶点的特殊工具，它们最终将成为新药。尽管最近取得了进展，但特定 RNA 结合剂的合理设计需要更好地了解与 RNA 靶标发生的相互作用，以达到所需的生物反应。在这篇综述中，我们讨论了探索这一尚未充分探索的化学空间所面临的挑战，以及最近结合、相互作用和影响生物学相关 RNA 的策略。