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

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 (

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2017
• Publication Date: Dec 1, 2017
• Deposit Date: Oct 24, 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
• Contract Date: Oct 24, 2017