GAS-PHASE NONCOVALENT INTERACTIONS BETWEEN VANCOMYCIN-GROUP ANTIBIOTICS AND BACTERIAL CELL-WALL PRECURSOR PEPTIDES PROBED BY HYDROGEN DEUTERIUM EXCHANGE/

Gas-phase structures of noncovalent complexes between the glycopeptide antibiotics vancomycin, eremomycin, ristocetin, and pseudo aglyco-ris tocetin acid the cell-wall mimicking peptides N-acetyl-D-Alanyl-D-Alan ine, 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 ND , as reagent gas. The noncovalent complexes were transferred from solu tion 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 an tibiotics and the free peptides were compared with the exchange observ ed for the antibiotic-peptide complexes. A general increase was found in the degree of deuterium incorporation upon complex formation with t he ligand, which indicates that the peptide binding makes more sites o n the antibiotic capable of taking part in the H/D exchange. Apart fro m H/D exchange, adduct formation with ND, was observed, but only for t he singly protonated peptides and the doubly protonated [ristocetin N-acetyl-D-Alanyl-D-Alanine]. This marked difference in chemical react ivity 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 sens itive 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 lon ger bound to the characteristic solution-phase binding pockets of the antibiotics. (C) 1998 American Society for Mass Spectrometry.