Structure based approaches for targeting non-coding RNAs with small molecules

• Published in: Current opinion in structural biology 2015-02, Vol.30, p.79-88
• Main Authors: Shortridge, Matthew D, Varani, Gabriele
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antiviral Agents - pharmacology; Biosynthetic Pathways - drug effects; Drug Discovery - methods; MicroRNAs - biosynthesis; MicroRNAs - chemistry; Models, Molecular; Molecular Structure; RNA, Untranslated - chemistry; RNA, Untranslated - metabolism; RNA, Untranslated - therapeutic use; Small Molecule Libraries - chemistry; Small Molecule Libraries - metabolism; Small Molecule Libraries - pharmacology
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2015.01.008

•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. 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.