Selective small-molecule inhibition of an RNA structural element.
Nature
; 526(7575): 672-7, 2015 Oct 29.
Article
in En
| MEDLINE
| ID: mdl-26416753
ABSTRACT
Riboswitches are non-coding RNA structures located in messenger RNAs that bind endogenous ligands, such as a specific metabolite or ion, to regulate gene expression. As such, riboswitches serve as a novel, yet largely unexploited, class of emerging drug targets. Demonstrating this potential, however, has proven difficult and is restricted to structurally similar antimetabolites and semi-synthetic analogues of their cognate ligand, thus greatly restricting the chemical space and selectivity sought for such inhibitors. Here we report the discovery and characterization of ribocil, a highly selective chemical modulator of bacterial riboflavin riboswitches, which was identified in a phenotypic screen and acts as a structurally distinct synthetic mimic of the natural ligand, flavin mononucleotide, to repress riboswitch-mediated ribB gene expression and inhibit bacterial cell growth. Our findings indicate that non-coding RNA structural elements may be more broadly targeted by synthetic small molecules than previously expected.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrimidines
/
RNA, Bacterial
/
Riboswitch
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nature
Year:
2015
Document type:
Article
Affiliation country:
Estados Unidos