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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
Deposit Date Oct 24, 2017
Publicly Available Date Mar 29, 2024
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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