Phenylethylene glycol-derived LpxC inhibitors with diverse Zn2+-binding groups
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چکیده
منابع مشابه
Characterization of LpxC Inhibitors and Resistant Mutants
Characterization of LpxC Inhibitors and Resistant Mutants by Daina Zeng Department of Biochemistry Duke University Date:_______________________ Approved: ___________________________ Pei Zhou, Supervisor ___________________________ Michael D. Been ___________________________ Kenneth N. Kreuzer ___________________________ Raphael H. Valdivia ___________________________ Robert A. Nicholas An abstr...
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LpxC, the deacetylase that catalyzes the second and committed step of lipid A biosynthesis in Escherichia coli, is an essential enzyme in virtually all gram-negative bacteria and is one of the most promising antibiotic targets for treatment of multidrug-resistant gram-negative infections. Despite the rapid development of LpxC-targeting antibiotics, the potential mechanisms of bacterial resistan...
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Lipid A is the hydrophobic anchor of lipopolysaccharide (LPS) and forms the major lipid component of the outer monolayer of the outer membrane of gram-negative bacteria. Lipid A is required for bacterial growth and virulence, and inhibition of its biosynthesis is lethal to bacteria. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metalloenzyme that catalyzes the secon...
متن کاملThe nucleotide-binding site of Aquifex aeolicus LpxC
The structure of recombinant Aquifex aeolicus UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) in complex with UDP has been determined to a resolution of 2.2 A. Previous studies have characterized the binding sites of the fatty-acid and sugar moieties of the substrate, UDP-(3-O-hydroxymyristoyl)-N-acetylglucosamine, but not that of the nucleotide. The uracil-binding site is constructed from ...
متن کاملAzetidinones as zinc-binding groups to design selective HDAC8 inhibitors.
2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone-r...
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ژورنال
عنوان ژورنال: Tetrahedron
سال: 2019
ISSN: 0040-4020
DOI: 10.1016/j.tet.2018.12.011