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利用RNA-蛋白质相互作用进行治疗干预。

Harnessing RNA-Protein Interactions for Therapeutic Interventions.

作者信息

Goel Khushboo, Saraogi Ishu

机构信息

Department of Chemistry, Indian Institute of Science Education and Research Bhopal Bhauri, Bhopal Bypass Road, Bhopal, Madhya Pradesh, 462066, India.

出版信息

Chem Asian J. 2025 Mar 3;20(5):e202401117. doi: 10.1002/asia.202401117. Epub 2025 Jan 5.

Abstract

Interactions between RNAs and proteins play a crucial role in various diseases, including viral infections and cancer. Hence, understanding and inhibiting these interactions are important for the development of novel therapeutics. However, the identification of drugs targeting RNA-protein interactions with high specificity and affinity is challenged by our limited molecular understanding of these interactions. Recent focus on structural and biochemical characterization, coupled with high-throughput screening technologies and computational modeling, have accelerated the identification of new RBPs and optimization of potential inhibitors. This review discusses key examples of inhibitors developed over the past decade that effectively disrupt pathogenic RNA-protein interactions. We focus on small molecule and peptide-based inhibitors that have shown promise in disrupting crucial RNA-protein interactions in eukaryotes, prokaryotes, and viruses. We also present the challenges and future directions in this field, emphasizing the need to achieve improved specificity and reduce the off-target effects of the inhibitors. This review aims to contribute to ongoing efforts towards the development of novel therapeutic agents targeting RNA-protein interactions by providing an in-depth analysis of significant developments and emerging trends in this rapidly growing field.

摘要

RNA与蛋白质之间的相互作用在包括病毒感染和癌症在内的各种疾病中起着至关重要的作用。因此,理解和抑制这些相互作用对于新型治疗方法的开发很重要。然而,由于我们对这些相互作用的分子理解有限,识别具有高特异性和亲和力的靶向RNA-蛋白质相互作用的药物面临挑战。最近对结构和生化特征的关注,结合高通量筛选技术和计算建模,加速了新的RNA结合蛋白(RBPs)的识别以及潜在抑制剂的优化。本综述讨论了过去十年中开发的有效破坏致病性RNA-蛋白质相互作用的抑制剂的关键实例。我们重点关注基于小分子和肽的抑制剂,这些抑制剂在破坏真核生物、原核生物和病毒中关键的RNA-蛋白质相互作用方面已显示出前景。我们还介绍了该领域的挑战和未来方向,强调需要提高特异性并减少抑制剂的脱靶效应。本综述旨在通过深入分析这一快速发展领域的重大进展和新趋势,为正在进行的靶向RNA-蛋白质相互作用的新型治疗药物的开发做出贡献。

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