Biophysical Analysis of Small Molecule Binding to Viral RNA Structures.
Biophysical Analysis of Small Molecule Binding to Viral RNA Structures.
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小分子与病毒 RNA 结构结合的生物物理分析。
DOI：
10.1007/978-1-0716-2695-5_16
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Tolbert,BlantonS
中科院分区：
文献类型：
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作者：
Chiu,Liang-Yuan;Davila-Calderon,Jesse;Cai,Zhengguo;Tolbert,BlantonS
RNA分子是携带遗传信息和调控基因表达的重要分子，在大多数生物体中，包括人类病原性RNA和相关的逆转录病毒。靶向病毒RNA（vRNA）结构为开发化学工具以探测分子病毒学和发现用于治疗干预的新靶点提供了广阔的机会。越来越多的RNA结合小分子被鉴定出来，激发了人们对RNA靶点小分子药物发现的兴趣。在本章中，我们描述了从vRNA样品制备开始表征和稳健验证vRNA-小分子（vRNA-sm）相互作用的方案，然后是针对vRNA靶点的小分子筛选，最后通过NMR光谱和量热滴定验证vRNA-sm相互作用。
RNA molecules are essential for carrying genetic information and regulating gene expression in most organisms including human pathogenic RNA and relate retro viruses. Targeting viral RNA (vRNA) structures provide broad opportunities to develop chemical tools to probe molecular virology and to discover novel targets for therapeutic intervention. An increasing number of RNA binding small molecules are being identified, stimulating increased interests in small molecule drug discovery for RNA targets. In this chapter, we describe protocols to characterize and robustly validate vRNA-small molecule (vRNA-sm) interactions starting from vRNA sample preparation, followed by small molecule screening against vRNA targets and finally to validating the vRNA-sm interactions via NMR spectroscopy and calorimetric titrations.