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Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches.

Biochemical Society transactions (2011-03-25)
Elena Cressina, Liuhong Chen, Michael Moulin, Finian J Leeper, Chris Abell, Alison G Smith
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Thiamine pyrophosphate, ≥95%
Supelco
Thiamine pyrophosphate, Pharmaceutical Secondary Standard; Certified Reference Material