Inhibition of Helicobacter pylori aminoacyl-tRNA amidotransferase by chloramphenicol analogs.
Bioorg Med Chem
; 18(22): 7868-72, 2010 Nov 15.
Article
in En
| MEDLINE
| ID: mdl-20943400
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Propanolamines
/
Chloramphenicol
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Helicobacter pylori
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Nitrogenous Group Transferases
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Enzyme Inhibitors
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Methionine
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Anti-Bacterial Agents
Language:
En
Year:
2010
Type:
Article