Objective

eIF4A is a DEAD box RNA helicase and ATPase. Using energy released from ATP hydrolysis, eIF4A resolves the secondary structure of the 5’ untranslated region on mRNA, such as G-quadruplexes and double stranded RNA elements. This activity is enhanced by the presence of eIF4G and eIF4B. Unwinding these longer, highly structured regions primes the mRNA and allows for the 40S ribosome subunit and associated factors to bind and initiate translation. In previous studies, it has been found that the target mRNAs of the eIF4A1 isoform are pro-proliferative and that inhibition of eIF4A1 has anti-cancer effects in cancerous cell lines such as breast, endometrial and cervical. Natural small molecule inhibitors of eIF4A have been previously identified with promising anti-cancer effects. As a part of our efforts to identify novel small molecule inhibitors, we have screened fragment libraries using differential scanning fluorimetry (DSF) against eIF4A and the scaffold protein eIF4G for fragments that bind to the complex.