Format

Send to

Choose Destination
Chem Biol. 2015 Apr 23;22(4):527-534. doi: 10.1016/j.chembiol.2015.03.016.

Small molecule fluoride toxicity agonists.

Author information

1
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
2
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
3
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. Electronic address: ronald.breaker@yale.edu.

Abstract

Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride.

PMID:
25910244
PMCID:
PMC4617673
DOI:
10.1016/j.chembiol.2015.03.016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center