The role of the sugar and chlorine substituents in the dimerization of vancomycin antibiotics

Gerhard, Ute; Mackay, Joel P.; Maplestone, Rachael A.; Williams, Dudley H.

doi:10.1021/ja00054a033

Cited by 177 publications

(147 citation statements)

References 2 publications

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“…The affinity constant for Aglu towards KAA was three times less than that of V, in agreement with data cited previously in the literature. [6,37] Aglu was found to have a higher affinity for LII than for KAA, nevertheless, it is still nearly 10 times lower than that of V.…”

Section: Resultsmentioning

confidence: 86%

“…For example, the sugar residues may positively influence glycopeptide binding to the bacterial cell wall, as well as possibly interfering with the trans-glycosylation process during the formation of the peptidoglycan. [6,38] Another factor that contributes to antibiotic efficacy is the possibility of noncovalent dimerization of some glycopeptide antibiotics. [39] It has been reported in the literature that cooperativity may induce glycopeptide antibiotics to dimerize upon binding to bacterial cell-wall analogues.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the sugars attached to the antibiotics may provide selectivity in binding cell-wall precursors terminating in d-Ala-d-Ala and are probably involved in stabilizing the dimer. [6] Glycopeptide antibiotics are not the only antimicrobials to use lipid II to weaken the structural integrity of the bacterial wall. Recently, it has been shown that nisin, a lanthionine- containing antibiotic, interacts with lipid II to form pores in the bacterial membrane leading to cell death.…”

Section: Introductionmentioning

confidence: 99%

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Getting Closer to the Real Bacterial Cell Wall Target: Biomolecular Interactions of Water‐Soluble Lipid II with Glycopeptide Antibiotics

Vollmerhaus

Breukink

Heck

2003

Chemistry A European J

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A novel synthesized watersoluble variant of lipid II (LII) was used to evaluate the noncovalent interactions between a number of glycopeptide antibiotics and their receptor by bioaffinity electrospray ionization mass spectrometry (ESI-MS). The water-soluble variant of lipid II is an improved design, compared to the traditionally used tripeptide, of the target molecule on the bacterial cell wall. A representative group of glycopeptide antibiotics was selected for this study to evaluate the validity of the novel cell-wall-mimicking target LII. Structure ± function relationships of various glycopeptide antibiotics were investigated by means of 1) bioaffinity mass spectrometry to evaluate solution-phase molecular interactions with both LII and KAA, 2) fluorescence leakage experiments to study the interactions with the membrane-embedded lipid II, and 3) minimum inhibitory concentrations against the indicator strain Micrococcus flavus. Our results with the novel LII molecule reveal that some antibiotics interact differently with KAA and LII. Additionally, our data cast doubt on the hypothesis that antibiotic selfdimerization assists in the invivo efficacy. Finally, the water-soluble lipid II proved to be a better model of the bacterial cell wall.

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Section: Resultsmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Getting Closer to the Real Bacterial Cell Wall Target: Biomolecular Interactions of Water‐Soluble Lipid II with Glycopeptide Antibiotics

Vollmerhaus

Breukink

Heck

2003

Chemistry A European J

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“…Since the disaccharide group shown in Figure 3 is not essential for the ligand recognition [33], derivatization of the dye on the primary amine of vancosamine is not expected to interfere with the complex hydrogen bond network. Based on our previous work on polyproline peptide dynamics in gas phase [1], BODIPY-R6G was coupled to vancosamine without a flexible linker to more closely reflect the conformational changes of the noncovalent complexes.…”

Section: Vancomycin-peptide Noncovalent Complexesmentioning

confidence: 99%

Fluorescence lifetime probe of biomolecular conformations

Shi¹,

Parks²

2010

J. Am. Soc. Mass Spectrom.

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Methods have been developed to measure the fluorescence lifetime versus temperature of trapped biomolecular ions derivatized with a fluorescent dye. Previous measurements for different sequences of polyproline peptides demonstrated that quenching rates are related to conformations and their spatial fluctuations. This paper presents the results of extending these methods to study the conformational dynamics of larger biomolecules. Vancomycin-peptide noncovalent complexes in the 1ϩ charge state were studied as a function of temperature for different W-KAA peptide chiralities (L-LDD, D-LDD, L-DLL). Fluorescence-quenching rates, k q , were found to be stereoselective for these different chiralities with relative magnitudesThe variation in fluorescent quenching resulting from switching the chirality of the single Trp residue was readily detectable. Molecular dynamics analysis of complexes formed by W-KAA (L-LDD) and W-KAA(L-DLL) indicates that increased flexibility in the (L-DLL) complex is correlated with reduced quenching rates. Fluorescence measurements were also performed for the Trp-cage protein comparing quenching rates in the 1ϩ, 2ϩ, and 3ϩ charge states for which k q. Measurements of a sequence including a single-point mutation infer the presence of a salt-bridge structure in the 1ϩ charge state and its absence in both the 2ϩ and 3ϩ states. Molecular dynamics structures of Trp-cage indicate that a salt bridge in the 1ϩ charge state produces more compact conformations leading to larger quenching rates based on the quenching mechanism. In both these experimental studies the fluorescence-quenching rates were consistent with changes in structure induced by either intermolecular or intramolecular interactions. (J Am Soc Mass Spectrom 2010, 21, 707-718) © 2010 American Society for Mass Spectrometry P revious measurements [1] of the lifetime of a fluorescent dye covalently bound to polypeptide ions exhibited a quenching rate that depends both on the separation of the dye to a Trp side chain and on the strength of electrostatic fields in the vicinity of the dye. Quenching rates were found to depend on specific peptide sequences giving rise to different conformations and spatial fluctuations characterized by each conformation. Consequently, lifetime measurements provide an opportunity to extract information sensitive to local molecular arrangements and, perhaps more importantly, changes in that arrangement determined by intramolecular and intermolecular interactions. This paper applies lifetime measurements to study two larger biomolecules: the vancomycin-peptide noncovalent complex and the Trp-cage protein. The structures of these biomolecules have been identified in NMR solution measurements; and each has been studied previously in gas-phase measurements. Results of gas-phase studies of the vancomycin-peptide complex infer that specific changes in the peptide ligand chirality lead to different hydrogen binding networks and thus to different conformations. Gas-phase measurements and calculations of Trp-cage protein i...

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“…It is noteworthy that the detection wavelength was set to 300 nm for avoiding high UV background at low wavelengths, when norvancomycin was present in the mobile phase. Previous studies showed that vancomycin and teicoplanin can form stable non-covalent dimmers or micelle in aqueous solutions [22,23], and this aggregation has been reported to influence positively or negatively the enantioseparation [24][25][26]. Improved chiral selectivity for flurbiprofen and FMOC-amino acid enantiomers was observed by Sun and Olesik when vancomycin was added to the mobile phase on a vancomycin-bonded chiral column (Chirobiotic-V) [27].…”

Section: Chiral Separation By Simultaneous Use Of Norvancomycin As Chmentioning

confidence: 98%

Chiral separation of enantiomers of amino acid derivatives by high-performance liquid chromatography on a norvancomycin-bonded chiral stationary phase

Ding

Liu

Cong

et al. 2004

Talanta

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The role of the sugar and chlorine substituents in the dimerization of vancomycin antibiotics

Abstract: Copyright 2007 Elsevier B.V., All rights reserved

Cited by 177 publications

References 2 publications

Getting Closer to the Real Bacterial Cell Wall Target: Biomolecular Interactions of Water‐Soluble Lipid II with Glycopeptide Antibiotics

Getting Closer to the Real Bacterial Cell Wall Target: Biomolecular Interactions of Water‐Soluble Lipid II with Glycopeptide Antibiotics

Fluorescence lifetime probe of biomolecular conformations

Chiral separation of enantiomers of amino acid derivatives by high-performance liquid chromatography on a norvancomycin-bonded chiral stationary phase

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