PMID:15134649
| Citation |
Ehmann, DE, Demeritt, JE, Hull, KG and Fisher, SL (2004) Biochemical characterization of an inhibitor of Escherichia coli UDP-N-acetylmuramyl-l-alanine ligase. Biochim. Biophys. Acta 1698:167-74 |
|---|---|
| Abstract |
UDP-N-acetylmuramyl-l-alanine ligase (MurC) is an essential bacterial enzyme involved in peptidoglycan biosynthesis and a target for the discovery of novel antibacterial agents. As a result of a high-throughput screen (HTS) against a chemical library for inhibitors of MurC, a series of benzofuran acyl-sulfonamides was identified as potential leads. One of these compounds, Compound A, inhibited Escherichia coli MurC with an IC(50) of 2.3 microM. Compound A exhibited time-dependent, partially reversible inhibition of E. coli MurC. Kinetic studies revealed a mode of inhibition consistent with the compound acting competitively with the MurC substrates ATP and UDP-N-acetyl-muramic acid (UNAM) with a K(i) of 4.5 microM against ATP and 6.3 microM against UNAM. Fluorescence binding experiments yielded a K(d) of 3.1 microM for the compound binding to MurC. Compound A also exhibited high-affinity binding to bovine serum albumin (BSA) as evidenced by a severe reduction in MurC inhibition upon addition of BSA. This finding is consistent with the high lipophilicity of the compound. Advancement of this compound series for further drug development will require reduction of albumin binding. |
| Links |
PubMed Online version:10.1016/j.bbapap.2003.11.006 |
| Keywords |
Benzofurans/chemistry; Benzofurans/pharmacology; Data Interpretation, Statistical; Escherichia coli/metabolism; Peptide Synthases/antagonists & inhibitors; Sulfonamides/chemistry; Sulfonamides/pharmacology; Uridine Diphosphate N-Acetylmuramic Acid/analogs & derivatives; Uridine Diphosphate N-Acetylmuramic Acid/metabolism |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.