Reaction of polycyclic hydrocarbon-cysteine conjugates with the aminoacyl-RNA synthetase system.

A number of arylcysteine derivatives, which are metabolites of polycyclic aromatic hydrocarbons, have been synthesized. These amino acid analogs were tested for their ability to act as substrates for aminoacyl-RNA synthetases in an in vitro system using enzyme fractions of bakers' yeast. These studies have shown that 5-(p-chlorophenyl)-L-cysteine, 5-(9 ,10 dihydro-9-hydroxy-l 0-phenanthryl)-L-cysteine, 5-(5 , 6-dihydro-6-hydroxy-5-benz(a)anthryl)-L -cysteine, 5(5 , 6dihydro-6-hydroxy-5-dibenz(a , h)anthrylL-cysteine, and S-(7-benz(a)anthryl)-methyl-L-cysteine are activated and transferred to tRNA. The arylcysteines were observed to compete with a variety of natural amino acids. This investi gation revealed that chlorophenylcysteine competed with arginine; dihydrohydroxyphenanthrylcysteine competed with glutamic acid, phenylalanine, and histidine for activating enzymes; dihydrohydroxybenzanthrylcysteine likewise com peted with arginine and phenylalanine; and dihydrohydroxydibenzanthrylcysteine competed with methionine and leucine. Thus, the structure of the hydrocarbon moiety conjugated with the sulfhydryl group of cysteine determines in particular the synthetases involved in amino acid activation. Moreover none of the cysteine conjugates were activated by the cysteinyl-RNA synthetase. Hydrocarbons are bound to protein by this pathway at sites different from those resulting from direct interaction.