Inhibition of Helicobacter pylori aminoacyl-tRNA amidotransferase by chloramphenicol analogs
| Autor: | Jonathan L. Huot, Christian Balg, Robert Chênevert, Sébastien P. Blais, Jacques Lapointe, Maria De Mieri |
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| Rok vydání: | 2010 |
| Předmět: |
Nitrogenous Group Transferases
Clinical Biochemistry Pharmaceutical Science Biochemistry Propanolamines chemistry.chemical_compound Non-competitive inhibition Methionine Drug Discovery medicine Enzyme Inhibitors Molecular Biology Antibacterial agent Glutamine amidotransferase chemistry.chemical_classification Aminoacyl-tRNA biology Helicobacter pylori Chemistry Chloramphenicol Organic Chemistry biology.organism_classification Anti-Bacterial Agents Enzyme Puromycin Molecular Medicine Bacteria medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry. 18(22) |
| ISSN: | 1464-3391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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