Gas-phase noncovalent interactions between vancomycin-group antibiotics and bacterial cell-wall precursor peptides probed by hydrogen/deuterium exchange

A. J.R. Heck*, T. J.D. Jørgensen, M. O'Sullivan, M. von Raumer, P. J. Derrick

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Gas-phase structures of noncovalent complexes between the glycopeptide antibiotics vancomycin, eremomycin, ristocetin, and pseudo aglyco-ristocetin and the cell-wall mimicking peptides N-acetyl-D-Alanyl-D-Alanine, N-acetyl-Glycyl-D-Alanine, and N,N′-di-acetyl L-Lysyl-D-Alanyl-D-Alanine have been probed by hydrogen/deuterium (H/D) exchange using ND3 as reagent gas. The noncovalent complexes were transferred from solution to the vacuum using electrospray ionization. The H/D exchange of the solvent-free ions was studied in a Fourier transform ion cyclotron resonance mass spectrometer. The H/D exchange behavior of the free antibiotics and the free peptides were compared with the exchange observed for the antibiotic-peptide complexes. A general increase was found in the degree of deuterium incorporation upon complex formation with the ligand, which indicates that the peptide binding makes more sites on the antibiotic capable of taking part in the H/D exchange. Apart from H/D exchange, adduct formation with ND3 was observed, but only for the singly protonated peptides and the doubly protonated [ristocetin+N-acetyl-D-Alanyl-D-Alanine]. This marked difference in chemical reactivity of closely related systems such as [ristocetin+N-acetyl-Glycyl-D-Alanine] and [ristocetin+N-acetyl-D-Alanyl-D-Alanine] indicates that the gas-phase structures of these noncovalent complexes are quite sensitive to small changes in the primary structures of the peptides. The gas-phase structures of the antibiotic-peptide complexes are probably different from the solution-phase structures, with the peptides no longer bound to the characteristic solution-phase binding pockets of the antibiotics.

Original languageEnglish
Pages (from-to)1255-1266
Number of pages12
JournalJournal of the American Society for Mass Spectrometry
Volume9
Issue number12
DOIs
Publication statusPublished - 1998
Externally publishedYes

Bibliographical note

Funding Information:
The University of Warwick FT-ICR facility is an UK national facility supported by the EPSRC (grant no. GR/K42042) and BBSRC (grant no. E00682). MvR was supported by the Swiss National Science Foundation.

Funding

The University of Warwick FT-ICR facility is an UK national facility supported by the EPSRC (grant no. GR/K42042) and BBSRC (grant no. E00682). MvR was supported by the Swiss National Science Foundation.

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