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Targeting RNA with Small Molecules

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Abstract:

Therapeutic targeting of RNA is not as well-developed as with DNA and proteins, and the many structures and functions of RNA suggest that it is an underutilized target. As with DNA, RNA has heterocyclic bases and base pairs with a highly anionic backbone, but as with proteins, RNA can fold into complex tertiary structures that create unique binding pockets for small molecules. Aminoglycoside targeting of ribosomal RNA is a well-known success story, and mRNAs and tRNAs have also served as therapeutic targets as well as model systems for understanding RNA-ligand interactions. The unique, species-specific structures and chemistry involved in splicing and ribozyme activity makes this RNA function an attractive target, and inhibitors of ribozyme activity have been discovered. The numerous serious human diseases caused by RNA viruses highlight the importance of developing new compounds that can target RNA structures in viral genomes. Considerable effort has been directed at finding compounds that target HIV-1 RNAs that control viral replication and frameshifting. As part of these efforts very useful new assays have been developed for small molecule-RNA interactions. The assays have led to the discovery of new inhibitors for different steps in viral replication. The next phase of research in RNA targeting will not only focus on the discovery of new compounds, but also on how to develop small molecules with high affinity and selectively for RNA that can penetrate effectively into a wide array of cell types.
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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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