Screening method for identifying new aminoacyl-trna synthetase inhibitors

Abstract

The method comprising: a) obtaining a gene sequence codifying a naturally occurring aminoacyl-tRNA synthetase; b) engineering the gene codifying for said aminoacyl-tRNA synthetase, resulting into an aminoacyl-tRNA synthetase with a defective activity, with the proviso that the engineering does not affect the functionality of the catalytic site of the enzyme; c) cloning the gene resulting from step (b) in an expression vector; d) transforming isolated mammalian cells with the expression vector resulting from step (c); e) growing the recombinant cells resulting from step (d) in a nutrient medium under conditions which allow the expression of the engineered aminoacyl-tRNA synthetase, resulting the expression into cell death or a decrease in the rate of cell division; f) providing a substance to be tested to the medium resulting from step (e); and g) analyzing the resulting cell growth, wherein if there is an increase in cell growth, then the substance selectively inhibits the activity of the engineered aminoacyl-tRNA synthetase and does not affect to its cellular ortholog, resulting in that said substance is a candidate to drug.