Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration
The reversibility and strength of the previously established dimerization of the important glycopeptide antibiotic vancomycin in four different aqueous solvents (including a medically-used formulation) have been studied using short-column sedimentation equilibrium in the analytical ultracentrifuge a...
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Nature
2017
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| Online Access: | https://eprints.nottingham.ac.uk/47166/ |
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| author | Phillips-Jones, Mary K. Lithgo, Ryan Dinu, Vlad Gillis, Richard B. Harding, John E. Adams, Gary G. Harding, Stephen E. |
| author_facet | Phillips-Jones, Mary K. Lithgo, Ryan Dinu, Vlad Gillis, Richard B. Harding, John E. Adams, Gary G. Harding, Stephen E. |
| author_sort | Phillips-Jones, Mary K. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The reversibility and strength of the previously established dimerization of the important glycopeptide antibiotic vancomycin in four different aqueous solvents (including a medically-used formulation) have been studied using short-column sedimentation equilibrium in the analytical ultracentrifuge and model-independent SEDFIT-MSTAR analysis across a range of loading concentrations. The change in the weight average molar mass Mw with loading concentration was consistent with a monomer-dimer equilibrium. Overlap of data sets of point weight average molar masses Mw(r) versus local concentration c(r) for different loading concentrations demonstrated a completely reversible equilibrium process. At the clinical infusion concentration of 5 mg.mL−1 all glycopeptide is dimerized whilst at 19 μg.mL−1 (a clinical target trough serum concentration), vancomycin was mainly monomeric (<20% dimerized). Analysis of the variation of Mw with loading concentration revealed dissociation constants in the range 25-75 μM, commensurate with a relatively weak association. The effect of two-fold vancomycin (19 μg. mL−1) appears to have no effect on the monomeric enterococcal VanS kinase involved in glycopeptide resistance regulation. Therefore, the 30% increase in sedimentation coefficient of VanS on adding vancomycin observed previously is more likely to be due to a ligand-induced conformational change of VanS to a more compact form rather than a ligand-induced dimerization. |
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| format | Article |
| id | nottingham-47166 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T20:04:32Z |
| publishDate | 2017 |
| publisher | Nature |
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| spelling | nottingham-471662024-08-15T15:24:19Z https://eprints.nottingham.ac.uk/47166/ Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration Phillips-Jones, Mary K. Lithgo, Ryan Dinu, Vlad Gillis, Richard B. Harding, John E. Adams, Gary G. Harding, Stephen E. The reversibility and strength of the previously established dimerization of the important glycopeptide antibiotic vancomycin in four different aqueous solvents (including a medically-used formulation) have been studied using short-column sedimentation equilibrium in the analytical ultracentrifuge and model-independent SEDFIT-MSTAR analysis across a range of loading concentrations. The change in the weight average molar mass Mw with loading concentration was consistent with a monomer-dimer equilibrium. Overlap of data sets of point weight average molar masses Mw(r) versus local concentration c(r) for different loading concentrations demonstrated a completely reversible equilibrium process. At the clinical infusion concentration of 5 mg.mL−1 all glycopeptide is dimerized whilst at 19 μg.mL−1 (a clinical target trough serum concentration), vancomycin was mainly monomeric (<20% dimerized). Analysis of the variation of Mw with loading concentration revealed dissociation constants in the range 25-75 μM, commensurate with a relatively weak association. The effect of two-fold vancomycin (19 μg. mL−1) appears to have no effect on the monomeric enterococcal VanS kinase involved in glycopeptide resistance regulation. Therefore, the 30% increase in sedimentation coefficient of VanS on adding vancomycin observed previously is more likely to be due to a ligand-induced conformational change of VanS to a more compact form rather than a ligand-induced dimerization. Nature 2017-10-05 Article PeerReviewed Phillips-Jones, Mary K., Lithgo, Ryan, Dinu, Vlad, Gillis, Richard B., Harding, John E., Adams, Gary G. and Harding, Stephen E. (2017) Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration. Scientific Reports, 7 (12697). pp. 1-10. ISSN 2045-2322 Biopolymers in vivo Physical chemistry https://www.nature.com/articles/s41598-017-12620-z doi:10.1038/s41598-017-12620-z doi:10.1038/s41598-017-12620-z |
| spellingShingle | Biopolymers in vivo Physical chemistry Phillips-Jones, Mary K. Lithgo, Ryan Dinu, Vlad Gillis, Richard B. Harding, John E. Adams, Gary G. Harding, Stephen E. Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration |
| title | Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration |
| title_full | Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration |
| title_fullStr | Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration |
| title_full_unstemmed | Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration |
| title_short | Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration |
| title_sort | full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with vans monomers at clinical concentration |
| topic | Biopolymers in vivo Physical chemistry |
| url | https://eprints.nottingham.ac.uk/47166/ https://eprints.nottingham.ac.uk/47166/ https://eprints.nottingham.ac.uk/47166/ |