Parasite-specific interaction of N-[4-(4'nitroanilino)-phenyl]-S-(beta-carboxyethyl)-dithiocar bamic acid-ester with arginyl-tRNA-synthetase from Dirofilaria immitis.
A potent inhibition of arginyl-tRNA-synthetase from Dirofilaria immitis by N-[4-(4'nitroanilino)-phenyl]-S-(beta-carboxylethyl)-dith iocarbamic acid-ester (CGP 8065) is demonstrated, which indicates the charging of amino acids to tRNA as a possible target for the chemotherapeutic attack by this filaricidal compound. CGP 8065 competes with ATP; the inhibition constant was determined to be 13 micrograms ml-1 (34 microM). The Michaelis constants for arginine and ATP were found to be 5 microM and 0.4 mM, respectively. The inhibition of arginyl-tRNA-synthetase by CGP 8065 was shown to be specific for D. immitis; the isofunctional enzymes from Ascaris suum and rat liver were not affected.
D000604:Amino Acyl-tRNA Synthetases; D000818:Animals; D000871:Anthelmintics; D001126:Arginine-tRNA Ligase; D001200:Ascaris / Q000201:enzymology; D004183:Dirofilaria immitis / Q000201:enzymology*; D005370:Filarioidea / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D051381:Rats; D013045:Species Specificity; D013859:Thiocarbamates
D000871:Anthelmintics; D013859:Thiocarbamates; C045009:CGP 8065; D000604:Amino Acyl-tRNA Synthetases; D001126:Arginine-tRNA Ligase