A fragment-based approach to identifying ligands for riboswitches.

Riboswitches are regions of mRNA that directly bind metabolites, leading to alteration of gene expression. We have developed fragment-based methods to screen for compounds that bind the Escherichia coli thiM riboswitch. Using complementary biophysical techniques we have identified several ligands with K(D) <100 microM. From these there is the potential to develop potent and selective modulators of riboswitch function.