Thermodynamics of interactions of vancomycin and synthetic surrogates of bacterial cell wall

Mikhail Rekharsky, Dusan Hesek, Mijoon Lee, Samy Meroueh, Yoshihisa Inoue, Shahriar Mobashery

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Glycopeptide antibiotics, including vancomycin, form complexes via a set of five hydrogen bonds with the acyl-L-Lys-D-Ala-D-Ala portion of the peptidyl stems of the bacterial cell wall peptidoglycan. This complexation deprives the organism from the ability to cross-link peptidyl stems of the peptidoglycan, leading to bacterial cell death. Four synthetic fragments as surrogates of the components of the bacterial cell wall have been prepared in our lab in multistep syntheses. These synthetic samples were used in investigations of the thermodynamics properties (ΔG°, ΔH°, and TΔS°) for the complexation with vancomycin by isothermal titration calorimetry (ITC). Complexation with the glycopeptide analogues is largely enthalpy-driven (formation of five hydrogen bonds), and in the analogues with a single peptidyl stem, the complexation is 1:1. The complexation is more complicated with an approximately 2 kDa cell wall surrogate (compound 4), which possesses two peptidyl stems. The data were suggestive of interactions between the two vancomycin molecules, with an entropic penalty attributable to restriction of molecular movements within the complex due to restriction of motion of the highly mobile acyl-D-Ala-D-Ala moiety of the peptidyl stems. These data were reconciled with the recently determined NMR solution structure for the peptidoglycan fragment 4 and its implications for the larger cell wall.

Original languageEnglish (US)
Pages (from-to)7736-7737
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number24
DOIs
StatePublished - Jun 21 2006
Externally publishedYes

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Vancomycin
Complexation
Thermodynamics
Cell Wall
Peptidoglycan
Cells
Glycopeptides
Hydrogen
Hydrogen bonds
Calorimetry
Antibiotics
Cell death
Cell Death
Titration
Stem Cells
Anti-Bacterial Agents
Enthalpy
Thermodynamic properties
Nuclear magnetic resonance
Molecules

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Thermodynamics of interactions of vancomycin and synthetic surrogates of bacterial cell wall. / Rekharsky, Mikhail; Hesek, Dusan; Lee, Mijoon; Meroueh, Samy; Inoue, Yoshihisa; Mobashery, Shahriar.

In: Journal of the American Chemical Society, Vol. 128, No. 24, 21.06.2006, p. 7736-7737.

Research output: Contribution to journalArticle

Rekharsky, Mikhail ; Hesek, Dusan ; Lee, Mijoon ; Meroueh, Samy ; Inoue, Yoshihisa ; Mobashery, Shahriar. / Thermodynamics of interactions of vancomycin and synthetic surrogates of bacterial cell wall. In: Journal of the American Chemical Society. 2006 ; Vol. 128, No. 24. pp. 7736-7737.
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