Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Wednesday 21st October 2020 from 07:00 AM to 07:00 PM (BST).

During this time our website performance may be temporarily affected. We apologise for any inconvenience this might cause and thank you for your patience.

Issue 1, 2011
Previous Article Next Article

Fragment screening against the thiamine pyrophosphate riboswitchthiM

Author affiliations


Riboswitches are regions of mRNA that bind selectively certain metabolites, thereby regulating gene expression. We have developed a method, which uses a combination of biophysical techniques (equilibrium dialysis, waterLOGSY and T2 relaxation-edited NMR spectroscopy and isothermal titration calorimetry) that allows screening and identification of novel ligands for riboswitches. By this method a library of 1300 fragments was screened on the E. colithiamine pyrophosphate (TPP) riboswitchthiM, resulting in the identification of 17 hits. The compounds showed KD values from 22 to 670 μM, with four compounds having KD values <100 μM. The fragments are structurally diverse and their ligand efficiency indicates good prospects for structure-guided elaboration. In addition, a riboswitch functional assay based on in vitrotranscription translation (IVTT) of the reporter gene luciferase was developed. This assay system is an alternative to in vivo assays and constitutes a valuable tool to determine the effect of small molecules on riboswitch-regulated gene expression.

Graphical abstract: Fragment screening against the thiamine pyrophosphate riboswitchthiM

Back to tab navigation

Supplementary files

Article information

02 Aug 2010
25 Aug 2010
First published
04 Oct 2010

Chem. Sci., 2011,2, 157-165
Article type
Edge Article

Fragment screening against the thiamine pyrophosphate riboswitchthiM

E. Cressina, L. Chen, C. Abell, F. J. Leeper and A. G. Smith, Chem. Sci., 2011, 2, 157
DOI: 10.1039/C0SC00406E

Social activity

Search articles by author