Bioorganic & Medicinal Chemistry 2005-01-03

Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate analogs.

Stéphane Bernier, Pierre-Marie Akochy, Jacques Lapointe, Robert Chênevert

Index: Bioorg. Med. Chem. 13(1) , 69-75, (2005)

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Abstract

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 (K(i) = 15 nM) whereas L-aspartol adenylate is a weaker inhibitor (K(i) = 45 microM) with respect to aspartic acid. The corresponding ketomethylphosphonate (a novel isosteric replacement) is also a strong inhibitor (K(i) = 123 nM).