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Title: Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues

Abstract

Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex.

Authors:
; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
939024
Report Number(s):
PNNL-SA-56291
Journal ID: ISSN 0002-7863; JACSAT; 17499a; 19802; 17499; KC0302020; TRN: US0806078
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of the American Chemical Society, 130(39):13013-13022
Additional Journal Information:
Journal Volume: 130; Journal Issue: 39; Journal ID: ISSN 0002-7863
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS; ANTIBIOTICS; BINDING ENERGY; CELL WALL; DISSOCIATION; EFFICIENCY; ELECTRONIC STRUCTURE; FRAGMENTATION; ION CYCLOTRON-RESONANCE; MASS SPECTROMETERS; PEPTIDES; PRECURSOR; PROTONS; SIMULATION; Environmental Molecular Sciences Laboratory

Citation Formats

Yang, Zhibo, Vorpagel, Erich R, and Laskin, Julia. Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues. United States: N. p., 2008. Web. doi:10.1021/ja802643g.
Yang, Zhibo, Vorpagel, Erich R, & Laskin, Julia. Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues. United States. https://doi.org/10.1021/ja802643g
Yang, Zhibo, Vorpagel, Erich R, and Laskin, Julia. 2008. "Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues". United States. https://doi.org/10.1021/ja802643g.
@article{osti_939024,
title = {Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues},
author = {Yang, Zhibo and Vorpagel, Erich R and Laskin, Julia},
abstractNote = {Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex.},
doi = {10.1021/ja802643g},
url = {https://www.osti.gov/biblio/939024}, journal = {Journal of the American Chemical Society, 130(39):13013-13022},
issn = {0002-7863},
number = 39,
volume = 130,
place = {United States},
year = {Wed Oct 01 00:00:00 EDT 2008},
month = {Wed Oct 01 00:00:00 EDT 2008}
}