Dual Targeting Antibacterial Peptide Inhibitor of Early Lipid A Biosynthesis
نویسندگان
چکیده
منابع مشابه
Antibacterial drug leads targeting isoprenoid biosynthesis.
With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The in...
متن کاملAncestral lipid biosynthesis and early membrane evolution.
Archaea possess unique membrane phospholipids that generally comprise isoprenoid ethers built on sn-glycerol-1-phosphate (G1P). By contrast, bacterial and eukaryal membrane phospholipids are fatty acid esters linked to sn-glycerol-3-phosphate (G3P). The two key dehydrogenase enzymes that produce G1P and G3P, G1PDH and G3PDH, respectively, are not homologous. Various models propose that these en...
متن کاملHIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis.
We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the x-ray cr...
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A structure-guided drug design approach was used to optimize a novel series of aminobenzimidazoles that inhibit the essential ATPase activities of bacterial DNA gyrase and topoisomerase IV and that show potent activities against a variety of bacterial pathogens. Two such compounds, VRT-125853 and VRT-752586, were characterized for their target specificities and preferences in bacteria. In metab...
متن کاملNGR-peptide−drug conjugates with dual targeting properties
Peptides containing the asparagine-glycine-arginine (NGR) motif are recognized by CD13/aminopeptidase N (APN) receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integ...
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ژورنال
عنوان ژورنال: ACS Chemical Biology
سال: 2012
ISSN: 1554-8929,1554-8937
DOI: 10.1021/cb300094a