PHARMACOLOGICAL TARGETING OF mRNA CAP FORMATION.

摘要

This invention provides methods for the discovery of molecules that target an essential aspect of eukaryotic gene expression - the formation of the mRNA 5' cap m7GpppN. An underlying principle of this invention is the use of different strains of a test organism that differ only in the composition or source of the essential cap-forming enzymes. The invention provides isogenic yeast strains that derive all their capping activities from fungal sources versus mammalian sources. These strains form the basis of a differential growth inhibition assay to identify molecules that specifically target the fungal capping apparatus. This invention also provides a method to screen in vitro for molecules that inhibit fungal RNA triphosphatase, an essential enzyme that catalyzes the first of three steps in cap synthesis.