Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, 130 Scripps Way, Jupiter, FL 33458, USA.
Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, 130 Scripps Way, Jupiter, FL 33458, USA; The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
Trends Pharmacol Sci. 2024 May;45(5):449-463. doi: 10.1016/j.tips.2024.03.006. Epub 2024 Apr 18.
RNA has diverse cellular functionality, including regulating gene expression, protein translation, and cellular response to stimuli, due to its intricate structures. Over the past decade, small molecules have been discovered that target functional structures within cellular RNAs and modulate their function. Simple binding, however, is often insufficient, resulting in low or even no biological activity. To overcome this challenge, heterobifunctional compounds have been developed that can covalently bind to the RNA target, alter RNA sequence, or induce its cleavage. Herein, we review the recent progress in the field of RNA-targeted heterobifunctional compounds using representative case studies. We identify critical gaps and limitations and propose a strategic pathway for future developments of RNA-targeted molecules with augmented functionalities.
RNA 具有多种细胞功能，包括调节基因表达、蛋白质翻译和细胞对刺激的反应，这要归功于其复杂的结构。在过去的十年中，已经发现了一些小分子，它们可以靶向细胞内 RNA 的功能结构并调节其功能。然而，简单的结合通常是不够的，导致生物活性低甚至没有。为了克服这一挑战，已经开发了杂双功能化合物，它可以与 RNA 靶标共价结合，改变 RNA 序列或诱导其切割。在此，我们通过代表性的案例研究，综述了 RNA 靶向杂双功能化合物领域的最新进展。我们确定了关键的差距和局限性，并提出了一个具有增强功能的 RNA 靶向分子的未来发展的战略途径。
