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.

Abstract

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 ?g.mL?1 (a clinical target trough serum concentration), vancomycin was mainly monomeric (

Citation

Phillips-Jones, M. K., Lithgo, R., Dinu, V., Gillis, R. B., Harding, J. E., Adams, G. G., & 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), 1-10. https://doi.org/10.1038/s41598-017-12620-z

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2017
• Online Publication Date: Oct 5, 2017
• Publication Date: 2017-12
• Deposit Date: Oct 11, 2017
• Publicly Available Date: Oct 11, 2017
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 1
• Article Number: 12697
• Pages: 1-10
• DOI: https://doi.org/10.1038/s41598-017-12620-z
• Keywords: Biopolymers in vivo, Physical chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/886309
• Publisher URL: https://www.nature.com/articles/s41598-017-12620-z