title: Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches.
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.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 3EW, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Cressina
authors.forename: Liuhong
authors.initials: L
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Moulin
authors.forename: Finian J
authors.initials: FJ
authors.lastname: Leeper
authors.forename: Chris
authors.initials: C
authors.lastname: Abell
authors.forename: Alison G
authors.initials: AG
authors.lastname: Smith
mesh_terms: D000818:Animals; D001483:Base Sequence; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D058928:Riboswitch / Q000502:physiology; D054852:Small Molecule Libraries / Q000032:analysis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013835:Thiamine Pyrophosphate / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D058928:Riboswitch; D054852:Small Molecule Libraries; D013835:Thiamine Pyrophosphate