Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches

Biochem Soc Trans. 2011 Apr;39(2):652-7. doi: 10.1042/BST0390652.


Riboswitches are regions of mRNA to which a metabolite binds in the absence of proteins, resoulting in alteration of transcription, translation or splicing. The most widespread forms of riboswitches are those responsive to TPP (thiamine pyrophosphate) the active form of vitamin B1, thiamine. TPP-riboswitches have been found in all bacterial genomes examined, and are the only ones found in eukaryotes. In each case, the riboswitch appears to regulate the expression of a gene involved in synthesis or uptake of the vitamin. Riboswitches offer an attractive target for chemical intervention, and identification of novel ligands would allow a detailed study on structure-activity relationships, as well as potential leads for the development of antimicrobial compounds. To this end, we have developed a medium-throughput methodology for screening libraries of small molecules using biophysical methods.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • High-Throughput Screening Assays / methods*
  • Humans
  • Ligands*
  • Models, Biological
  • Models, Molecular
  • Nucleic Acid Conformation
  • Riboswitch* / physiology
  • Small Molecule Libraries / analysis
  • Small Molecule Libraries / chemistry
  • Structure-Activity Relationship
  • Thiamine Pyrophosphate / chemistry
  • Thiamine Pyrophosphate / metabolism*


  • Ligands
  • Riboswitch
  • Small Molecule Libraries
  • Thiamine Pyrophosphate