Article ; Online: Small molecule targeting of biologically relevant RNA tertiary and quaternary structures.
Cell chemical biology
2021 Volume 28, Issue 5, Page(s) 594–609
Abstract: Initial successes in developing small molecule ligands for non-coding RNAs have underscored their potential as therapeutic targets. More recently, these successes have been aided by advances in biophysical and structural techniques for identification and ...
Abstract | Initial successes in developing small molecule ligands for non-coding RNAs have underscored their potential as therapeutic targets. More recently, these successes have been aided by advances in biophysical and structural techniques for identification and characterization of more complex RNA structures; these higher-level folds present protein-like binding pockets that offer opportunities to design small molecules that could achieve a degree of selectivity often hard to obtain at the primary and secondary structure level. More specifically, identification and small molecule targeting of RNA tertiary and quaternary structures have allowed researchers to probe several human diseases and have resulted in promising clinical candidates. In this review we highlight a selection of diverse and exciting successes and the experimental approaches that led to their discovery. These studies include examples of recent developments in RNA-centric assays and ligands that provide insight into the features responsible for the affinity and biological outcome of RNA-targeted chemical probes. This report highlights the potential and emerging opportunities to selectively target RNA tertiary and quaternary structures as a route to better understand and, ultimately, treat many diseases. |
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MeSH term(s) | Humans ; Ligands ; Nucleic Acid Conformation ; RNA/chemistry ; RNA/drug effects ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology |
Chemical Substances | Ligands ; Small Molecule Libraries ; RNA (63231-63-0) |
Language | English |
Publishing date | 2021-04-05 |
Publishing country | United States |
Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review |
ISSN | 2451-9448 |
ISSN (online) | 2451-9448 |
DOI | 10.1016/j.chembiol.2021.03.003 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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