Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate analogs Original Research Article

Three nonhydrolyzable aspartyl adenylate analogs have been prepared and tested as inhibitors of E. coli aspartyl-tRNA synthetase. 5′-O-[N-(l-Aspartyl)sulfamoyl]adenosine is a potent competitive inhibitor (Ki = 15 nM) whereas l-aspartol adenylate is a weaker inhibitor (Ki = 45 μM) with respect to aspartic acid. The corresponding ketomethylphosphonate (a novel isosteric replacement) is also a strong inhibitor (Ki = 123 nM).