Phenylalanyl transfer ribonucleic acid synthetase from Escherichia coli B. Potent inhibition by analogues of N-benzyl-2-phenylethylamine.
A potent new class of inhibitors of phenylalanyl-tRNA synthetase from Escherichia coli B is described. N-Benzyl-2-phenylethylamine is a competitive inhibitor with respect to L-phenylalanine and appears to possess the structural features required for near-optimal binding. Hydrophobic substituents at the ortho position of either ring appear to be well tolerated, but substituents on both rings lead to large losses in binding. Poor noncompetitive inhibitors resllt from alkylation of the secondary nitrogen, further separation of the N-benzyl group from the nitrogen, or alkylation at the alpha position of the N-benzyl moiety. In contrast, placement of a methyl group at the 1 position of the 2-phenylethylamine moiety to give N-benzyl-D-amphetamine results in the most potent inhibitor yet described for this enzyme.
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology*; D066298:In Vitro Techniques; D010627:Phenethylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D010652:Phenylalanine-tRNA Ligase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D010627:Phenethylamines; D000604:Amino Acyl-tRNA Synthetases; D010652:Phenylalanine-tRNA Ligase