Inhibition of phenylalanyl-tRNA synthetase by aromatic guanidines and amidines.

Aromatic guanidines and amidines were investigated for their ability to inhibit phenylalanyl-tRNA synthetase from E. coli B. 2-Phenylacetamidine (1), benzylguanidine (2), and N-benzylbenzamidine (3) are competive inhibitors with respect to phenylalanine, binding nearly as well as the substrate, The remainder of the inhibitors was unexpectedly found to be noncompetitive, indication the presence of a secondary binding site on the enzyme. Inhibition by these compounds appears to be specific for phenylalanyl-tRNA synthetase and requires the presence of a phenyl ring as well as the amidine or guanidine moiety.