Cooperativity in ligand binding expressed at a model cell membrane by the vancomycin group antibiotics

Westwell, Martin S.; Bardsley, Ben; Dancer, Robert J.; Try, Andrew C.; Williams, Dudley H.

doi:10.1039/cc9960000589

Cited by 42 publications

(54 citation statements)

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“…[71] Moreover, the chemical shift of w 2 (which was shown earlier to occur at lower field the more strongly the ligand was bound to it) in the latter assembly occurs further downfield (d 11.65) than for the former association (d 11.43). [71] Similar results were achieved for teicoplanin binding to the peptides Ac 2 -KdAdA and N-a-decanoyl-N-e-acetyl-lysyl-d-alanyl-d-alanine (DecKdAdA) in the presence of micelles. As for ristocetin A binding to Dec-dAdA and Ac-dAdA, the binding constant of teicoplanin to Dec-KdAdA was greater than that to Ac 2 -KdAdA and w 2 was shifted further downfield for the binding of Dec-KdAdA than for the binding of Ac 2 -KdAdA.…”

mentioning

confidence: 94%

“…As for ristocetin A binding to Dec-dAdA and Ac-dAdA, the binding constant of teicoplanin to Dec-KdAdA was greater than that to Ac 2 -KdAdA and w 2 was shifted further downfield for the binding of Dec-KdAdA than for the binding of Ac 2 -KdAdA. [71] Thus, in the formation of templated assemblies, not only is there the advantage of a relatively small adverse entropy (the binding being effectively intramolecular), but the motional restriction associated with binding at a template (the micelle surface) is also associated with stronger bonding of the peptide carboxylate into its receptor pocket.…”

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confidence: 95%

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The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria

Williams

Bardsley

1999

Angew. Chem. Int. Ed.

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confidence: 94%

mentioning

confidence: 95%

The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria

Williams

Bardsley

1999

Angew. Chem. Int. Ed.

Self Cite

490

351

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“…In the presence of doc-KAA, the binding of teicoplanin was also enhanced; attributed to cooperative binding of precursors analogues binding and membrane anchoring [10]. This explains why teicoplanin at lower concentrations also showed significant responses, whereas significant binding for vancomycin is only observed when concentrations are sufficient to lead to a dimer population at the membrane surface [33][34][35]37].…”

Section: Discussionmentioning

confidence: 67%

“…Teicoplanin binds to membranes in the absence of doc-KAA, due to the lipophilic C 11 acyl chain, which can serve as a membrane anchor to localize the antibiotic in the membrane [34,35]. The fatty acid chain enhances the lipophilicity of the compound partition coefficient (log P) of teicoplanin (À2.26), compared with vancomycin (À4.41) [36].…”

Section: Discussionmentioning

confidence: 98%

Affinities and in-plane stress forces between glycopeptide antibiotics and biomimetic bacterial membranes

Ranzoni

Huang

et al. 2015

Sensing and Bio-Sensing Research

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a b s t r a c tUnderstanding the molecular basis of interactions between antibiotics affecting bacterial cell wall biosynthesis and cellular membranes is important in rational drug design of new drugs to overcome resistance. However, a precise understanding of how bacteriostatic antibiotics effect action often neglects the effect of biophysical forces involved following antibiotic-receptor binding events. We have employed a combination of a label-free binding biosensor (surface plasmon resonance, SPR) and a force biosensor (in-plane stress cantilever), together with model membrane systems to study the complex interplay between glycopeptide antibiotics, their cognate ligands and different model membranes. Bacterial cell wall precursor analogue N-a-Docosanoyl-e-acetyl-Lys-D-Alanine-D-Alanine (doc-KAA) was inserted into lipid layers comprised of zwitterionic or anionic lipids then exposed to either vancomycin or the membrane-anchored glycopeptide antibiotic teicoplanin. Binding affinities and kinetics of the antibiotics to these model membranes were influenced by electrostatic interactions with the different lipid backgrounds, in addition to ligand affinities. In addition, cantilever sensors coated with model membranes showed that planar surface stress changes were induced by glycopeptide antibiotics adsorption and caused compressive surface stress generation in a ligand-dependent manner.

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“…1c and d) by an alkylation of a chlorobenzylphenyl side chain (green) at the 4-epi-vancomsamine on the fourth amino acid and an additional 4-epi-vancomsamine (purple) at the sixth amino acid of the aglycon. Since oritavancin readily forms dimers in solution and binds to membrane vesicles (8), drug dimerization and membrane anchoring mediated by the hydrophobic side chain of oritavancin are thought to increase its binding to the D-Ala-D-Lac-terminated PG stem structure to overcome the vancomycin resistance in VRE (9). However, in situ characterizations of oritavancin (10) and oritavancin-like glycopeptide (4,11,12) binding sites in intact whole cells of S. aureus by solid-state nuclear magnetic resonance (NMR) have shown that lipoglycopeptides do not bind to the cell wall as dimers or partition to the bacterial membrane.…”

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Inhibition of Staphylococcus aureus Cell Wall Biosynthesis by Desleucyl-Oritavancin: a Quantitative Peptidoglycan Composition Analysis by Mass Spectrometry

et al. 2017

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Oritavancin is a lipoglycopeptide antibiotic that exhibits potent activities against vancomycin-resistant Gram-positive pathogens. Oritavancin differs from vancomycin by a hydrophobic side chain attached to the drug disaccharide, which forms a secondary binding site to enable oritavancin binding to the cross-linked peptidoglycan in the cell wall. The mode of action of secondary binding site was investigated by measuring the changes in the peptidoglycan composition of Staphylococcus aureus grown in the presence of desleucyl-oritavancin at subinhibitory concentration using liquid chromatography-mass spectrometry (LC-MS). Desleucyl-oritavancin is an Edman degradation product of oritavancin that exhibits potent antibacterial activities despite the damaged D-Ala-D-Ala binding site due to its functional secondary binding site. Accurate quantitative peptidoglycan composition analysis based on 83 muropeptide ions determined that cell walls of S. aureus grown in the presence of desleucyl-oritavancin showed a reduction of peptidoglycan cross-linking, increased muropeptides with a tetrapeptide-stem structure, decreased O-acetylation of MurNAc, and increased N-deacetylation of GlcNAc. The changes in peptidoglycan composition suggest that desleucyl-oritavancin targets the peptidoglycan template to induce cell wall disorder and interferes with cell wall maturation.IMPORTANCE Oritavancin is a lipoglycopeptide antibiotic with a secondary binding site that targets the cross-linked peptidoglycan bridge structure in the cell wall. Even after the loss of its primary D-Ala-D-Ala binding site through Edman degradation, desleucyl-oritavancin exhibits potent antimicrobial activities through its still-functioning secondary binding site. In this study, we characterized the mode of action for desleucyl-oritavancin's secondary binding site using LC-MS. Peptidoglycan composition analysis of desleucyl-oritavancin-treated S. aureus was performed by determining the relative abundances of 83 muropeptide ions matched from a precalculated library through integrating extracted ion chromatograms. Our work highlights the use of quantitative peptidoglycan composition analysis by LC-MS to provide insights into the mode of action of glycopeptide antibiotics.

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Cooperativity in ligand binding expressed at a model cell membrane by the vancomycin group antibiotics

Abstract: Dimerisation or the use of a membrane anchor enhances the binding of the glycopeptide antibiotics at the surface of a model cell membrane.

Cited by 42 publications

References 9 publications

The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria

The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria

Affinities and in-plane stress forces between glycopeptide antibiotics and biomimetic bacterial membranes

Inhibition of Staphylococcus aureus Cell Wall Biosynthesis by Desleucyl-Oritavancin: a Quantitative Peptidoglycan Composition Analysis by Mass Spectrometry

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