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Tocris社 Targeting RNA with Small Molecules

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Targeting_RNA_with_Small_Molecules_Header.pngNon-coding RNAs, such as ribosomal RNAs and micro RNAs, fold into complex 3D structures, which are involved in key cellular processes such as protein translation, RNA splicing, DNA replication and regulation of gene expression. These diverse and central roles make RNA an attractive target for innovative drug discovery. In order to develop small molecules for RNA targets, structural information on the fold and flexibility of the RNA strand must be determined.

Learn more about RNA as a drug target in this paper in J. Med. Chem; How we think about targeting RNA with small molecules.  Costales et al (2020).

 

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Inhibits Formation of miR-210
Targapremir (Cat. No. 6586)

 

  • Inhibits formation of microRNA miR-210 by binding to the Dicer site of the miR-210 hairpin precursor (Kd ~ 200 nM)
  • Decreases levels of miR-210 and HIF-1α mRNA, and induces apoptosis in cells cultured under hypoxic conditions
  • Reduces tumor expression of HIF-1α mRNA and miR-210, and tumor growth in a triple negative breast cancer mouse model

Reagents for RNA SHAPE-MaP Chemistry

Selective 2'- Hydroxyl (2'-OH)  Acylation and Primer Extension (SHAPE) and SHAPE-MaP reagents are used for the determination of complex, secondary RNA structures formed by RNA forming base pairs with itself and its interaction with other molecules. Compounds such as NAI and 1M7 below, are rapidly absorbed into cells and react with RNA based on differences in 2'-OH reactivity of single- and double-stranded RNA. Reactivity differences allow researchers to distinguish between flexible and folded regions of RNA, enabling a deeper understanding of structural interactions that can be exploited for drug development. 

NAI (Cat. No. 7004)

  • Reagent for RNA SHAPE-MaP experiments in vivo
  • Acylates 2'-OH in RNA, labeling single-stranded or flexible regions more than folded regions
  • Requires quenching step
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1M7 (Cat. No. 6602)

  • Reagent for SHAPE-MaP experiments
  • Enables single nucleotide resolution in <70 seconds
  • Low nucleotide reactivity bias

 

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Learn more about SHAPE and SHAPE-MaP in this detailed review and protocol outline from Smola & Weeks, (2018)  In-cell RNA structure probing with SHAPE-MaP. Nature Protocols.

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