Objective

The DEAD-box RNA helicases present an exciting target class for disease therapy. Situated at the very core of translational regulation, unsurprisingly, several DEAD-box helicases are known targets for exploitation given they are precise tools for removing specific translational road blocks. eIF4A is the prototypical DEAD-box helicase that together with its homologs and other components form the multipartite complex eIF4F. Two major components of the eIF4F complex, eIF4A and eIF4G have been targeted in a drug discovery project to identify novel small molecule modulators of eIF4F activity. The approach we have taken has consisted of a plethora of biochemical and biophysical assays in efforts to screen a functionally relevant complex.