Inhibition of Helicobacter pylori aminoacyl-tRNA amidotransferase by chloramphenicol analogs

被引：20

作者：

Balg, Christian ^{[1
]}

De Mieri, Maria ^{[3
]}

Huot, Jonathan L. ^{[2
]}

Blais, Sebastien P. ^{[2
]}

Lapointe, Jacques ^{[2
]}

Chenevert, Robert ^{[1
]}

机构：

[1] Univ Laval, Fac Sci & Genie, PROTEO, Dept Chim, Quebec City, PQ G1V 0A6, Canada

[2] Univ Laval, Fac Sci & Genie, PROTEO, Dept Biochim & Microbiol, Quebec City, PQ G1V 0A6, Canada

[3] Univ Milan, Dipartimento Chim Biochim & Biotecnol Med, I-20133 Milan, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 22期

基金：

加拿大自然科学与工程研究理事会;

关键词：

Chloramphenicol; Amidotransferase; Aminoacyl-tRNA; Transamidation; GatCAB; Helicobacter pylori; Puromycin; STRUCTURAL BASIS; GLUTAMINE; GATCAB;

D O I：

10.1016/j.bmc.2010.09.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 = 2 mu M), with a K-i value of 27 mu M. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7868 / 7872

页数：5

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