4EGI-1 mimics the action of a class of cellular regulatory molecules that naturally inhibit the binding of two initiation factors necessary for interaction of transcribed mRNA with the subunits of ribosomal complexes.

[1] The Harvard research group leading the study screened 16,000 compounds, looking for one that would displace a fluorescein-labeled peptide derived from the eIF4G sequence that binds to the eIF4E form at the same site.

It appears that by displacing the eIF4G sequence without blocking the entire binding interface of eIF4E, 4EGI-1 is able to clear the “docking site” of the endogenous regulator.

Strong mRNAs, in contrast, are translated with much less cellular machinery such as eIFs and generally code for biologically necessary proteins, such as those needed for the essential metabolic processes of a cell.

Therapies such as the use of 4EGI-1 against cancer cells can thus be created such that their biologic targets include only the initiation factors involved in the production of weak mRNAs.

Cap-dependent translation involves a series of steps that join the small and large ribosomal subunits at the start codon of mRNA.

When attempting to identify biological molecules that would disrupt the formation of the F complex, researchers developed a high-throughput fluorescence polarization (FP)-binding assay.