Metal Ion-Peptide Interactions in the Gas Phase: A Tandem Mass Spectrometry Study of Alkali Metal Cationized Peptides

Fast atom bombardment combined with tandem mass spectrometry has been used to investigate the gas-phase interactions of alkali metal ions and small peptides. Alkali cations bind to peptides primarily at the C-terminus, promoting the loss of a C-terminal residue to give a peptide having one less amino acid. This novel fragmentation involving migration of an oxygen atom is general, occurs for metastable as well as for collisionally activated ions, and is the basis of a method to identify rapidly the C-terminal amino acid. The mechanism of decomposition is analogous to the cleavage of a C-terminal amino acid by the enzyme carboxypeptidase. In addition to the ions formed by loss of a residue of the C-terminal amino acid, another class of fragment ions of the type -CONHCHR^lCON⁺(Met)=CHR²(Met = alkali metal ion) is produced by collisional activation. The peptide-metal ion complex isomerizes upon collisional activation, forming a molecular species in which the metal ion is coordinated to a deprotonated amide nitrogen. These isomers lose both CO and an amino acid or small peptide, depending on the site of coordination, from the C-terminus to produce the metalated immonium ions. Although these ions are produced at low abundance when ions decompose metastably, they become dominant for collisionally activated peptides containing histidine residues. Formation of a stable six-member chelate ring involving the pyridine nitrogen of the imidazole ring of histidine accounts for their abundance. The final structure has bonding features that are analogous to those of transition metal ions and deprotonated amide nitrogens of peptides in solution.