Structure based approaches for targeting non-coding RNAs with small molecules. (February 2015)

• Record Type: Journal Article
• Authors: Shortridge, Matthew D; Varani, Gabriele
• Is Part Of: Current opinion in structural biology. Volume 30(2015)
• Page Start: 79
• Page End: 88
• Publication Date: 2015-02
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2015.01.008
• Languages: English
• ISSNs: 0959-440X

Abstract

Highlights: Non-coding RNAs provide new therapeutic targets to treat chronic conditions. Successful targeting by small molecules is dependent on RNA structural features. New rational methods to identify selective non-oligonucleotide inhibitors. Abstract : The increasing appreciation of the central role of non-coding RNAs (miRNAs and long non-coding RNAs) in chronic and degenerative human disease makes them attractive therapeutic targets. This would not be unprecedented: the bacterial ribosomal RNA is a mainstay for antibacterial treatment, while the conservation and functional importance of viral RNA regulatory elements has long suggested they would constitute attractive targets for new antivirals. Oligonucleotide-based chemistry has obvious appeals but also considerable pharmacological limitations that are yet to be addressed satisfactorily. Recent studies identifying small molecules targeting non-coding RNAs may provide an alternative approach to oligonucleotide methods. Here we review recent work investigating new structural and chemical principles for targeting RNA with small molecules.