Collision-induced dissociation of noncovalent complexes between vancomycinantibiotics and peptide ligand stereoisomers: Evidence for molecular recognition in the gas phase

In solution, the antibiotics of the vancomycin group bind stereospecificall y to peptides with the C-terminal sequence: -L-Lys-D-Ala-D-Ala, Substitutio n by a L-Ala at either of the two C-terminal residues causes a dramatic dec rease in the binding affinity to the antibiotics. This solution behavior is clearly reflected in electrospray ionization (ESI) mass spectra obtained f rom equimolar mixtures of an antibiotic, an isotopically labelled peptide l igand and an unlabelled peptide stereoisomer. Using collision-induced disso ciation (CID) we have probed the gas phase stability of isomeric (1:1) nonc ovalent complexes formed between vancomycin and tripeptide stereoisomers. I n negative ion mode the CID results show that a complex formed between vanc omycin and a -L-Ala-L-Ala ligand fragments more readily than a complex form ed between vancomycin and a -D-Ala-D-Ala ligand. This difference in gas pha se stability is in agreement with what would be expected if the noncovalent complexes had retained their structural specific interactions from solutio n to gas phase. In positive ion mode no significant difference in the gas p hase stabilities of the isomeric complexes could be observed. We attribute this similarity in gas phase stability between isomeric positively-charged complexes to a protonation of the C-terminus of the peptide ligand which de stroys the specific interaction between antibiotic and peptide ligand. Mole cular recognition phenomena in the gas phase were investigated by CID of mi xed cluster ions consisting of an antibiotic, a -L-Ala peptide, a -D-Ala st ereoisomer, one ligand isotopically labelled. Upon CID of the negatively ch arged mixed cluster ions a stereoselective loss of the assumed "nonspecific ally" bound -L-Ala ligand was observed. (Int J Mass Spectrom 188 (1999) 63- 85) (C) 1999 Elsevier Science B.V.