title: Synthesis and aminoacyl-tRNA synthetase inhibitory activity of aspartyl adenylate analogs.
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).
authors.affiliation: Département de chimie, Centre de recherche sur la fonction, la structure et l'ingénierie des protéines (CREFSIP), Faculté des sciences et de génie, Université Laval, Québec, Canada G1K 7P4.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bernier
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Akochy
authors.forename: Jacques
authors.initials: J
authors.lastname: Lapointe
authors.forename: Robert
authors.initials: R
authors.lastname: Chênevert
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
chemical_list: D004791:Enzyme Inhibitors; C052755:aspartyl adenylate; D001224:Aspartic Acid; D000249:Adenosine Monophosphate; D000604:Amino Acyl-tRNA Synthetases