Parasite-specific interaction of N-[4- (4'nitroanilino) -phenyl]-S- (beta-carboxyethyl) -dithiocar bamic acid-ester with arginyl-tRNA-synthetase from Dirofilaria immitis
Walter, R.D.; Kuhlow, F.
Tropical Medicine and Parasitology Official Organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft für Technische Zusammenarbeit 36(4): 230-232
1985
ISSN/ISBN: 0177-2392 PMID: 3841408 Document Number: 266731
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.