Inhibition of Helicobacter pylori aminoacyl-tRNA amidotransferase by chloramphenicol analogs.

Christian Balg, Maria De Mieri, Jonathan L Huot, Sébastien P Blais, Jacques Lapointe, Robert Chênevert

Département de Chimie, PROTEO, Faculté des Sciences et de Génie, Université Laval, Québec, Canada G1V 0A6.

Bioorganic & medicinal chemistry 2010 Nov 15

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Genomic studies revealed the absence of glutaminyl-tRNA synthetase and/or asparaginyl-tRNA synthetase in many bacteria and all known archaea. In these microorganisms, glutaminyl-tRNA(Gln) (Gln-tRNA(Gln)) and/or asparaginyl-tRNA(Asn) (Asn-tRNA(Asn)) are synthesized via an indirect pathway involving side chain amidation of misacylated glutamyl-tRNA(Gln) (Glu-tRNA(Gln)) and/or aspartyl-tRNA(Asn) (Asp-tRNA(Asn)) by an amidotransferase. A series of chloramphenicol analogs have been synthesized and evaluated as inhibitors of Helicobacter pylori GatCAB amidotransferase. Compound 7a was identified as the most active competitive inhibitor of the transamidase activity with respect to Asp-tRNA(Asn) (K(m)=2μM), with a K(i) value of 27μM. Copyright © 2010 Elsevier Ltd. All rights reserved.

Citation

Christian Balg, Maria De Mieri, Jonathan L Huot, Sébastien P Blais, Jacques Lapointe, Robert Chênevert. Inhibition of Helicobacter pylori aminoacyl-tRNA amidotransferase by chloramphenicol analogs. Bioorganic & medicinal chemistry. 2010 Nov 15;18(22):7868-72