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Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration

Phillips-Jones, Mary K.; Gillis, Richard B.; Adams, Gary G.; Harding, Stephen E.; Lithgo, Ryan; Harding, John E; Harding, Stephen E; DInu, Vlad

Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration Thumbnail


Authors

Mary K. Phillips-Jones

Richard B. Gillis

Gary G. Adams

Stephen E. Harding

Ryan Lithgo

John Harding John3.Harding@uwe.ac.uk
External Adviser / Panel Member - SAS

Stephen E Harding

Vlad DInu



Abstract

© 2017 The Author(s). 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-MST analysis across a range of loading concentrations. The change in the weight average molar mass M w with loading concentration was consistent with a monomer-dimer equilibrium. Overlap of data sets of point weight average molar masses M w(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 (

Citation

Harding, S. E., Adams, G. G., Gillis, R. B., Phillips-Jones, M. K., Lithgo, R., DInu, V., …Harding, S. 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(1), 12697. https://doi.org/10.1038/s41598-017-12620-z

Journal Article Type Article
Acceptance Date Aug 29, 2017
Publication Date Dec 1, 2017
Publicly Available Date Oct 24, 2017
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Nature Research (part of Springer Nature)
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
Pages 12697
DOI https://doi.org/10.1038/s41598-017-12620-z
Keywords full hydrodynamic reversibility, weak dimerization, vancomycin, elucidation, interaction, VanS monomers, clinical concentration
Public URL https://uwe-repository.worktribe.com/output/879887
Publisher URL http://dx.doi.org/10.1038/s41598-017-12620-z

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