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Gold(I) Cationization Promotes Ring Opening in Lysine-Containing Cyclic Peptides

Journal Article · · Journal of the American Society for Mass Spectrometry

A strategy to sequence lysine-containing cyclic peptides by MS{sup n} is presented. Doubly protonated cyclic peptides ions are transformed into gold (I) cationized peptide ions via cation switching ion/ion reaction. Gold(I) cationization facilitates the oxidation of neutral lysine residues in the gas phase, weakening the adjacent amide bond. Upon activation, facile cleavage N-terminal to the oxidized lysine residue provides a site-specific ring opening pathway that converts cyclic peptides into acyclic analogs. The ensuing ion contains a cyclic imine as the new N-terminus and an oxazolone, or structural equivalent, as the new C-terminus. Product ions are formed from subsequent fragmentation events of the linearized peptide ion. Such an approach simplifies MS/MS data interpretation as a series of fragment ions with common N- and C-termini are generated. Results are presented for two cyclic peptides, sunflower trypsin inhibitor and the model cyclic peptide, β-Loop. The power of this strategy lies in the ability to generate the oxidized peptide, which is easily identified via the loss of HAuNH{sub 3} from [M + Au]{sup +}. While some competitive processes are observed, the site of ring opening can be pinpointed to the lysine residue upon MS{sup 4} enabling the unambiguous sequencing of cyclic peptides. .

OSTI ID:
22925081
Journal Information:
Journal of the American Society for Mass Spectrometry, Journal Name: Journal of the American Society for Mass Spectrometry Journal Issue: 10 Vol. 30; ISSN 1044-0305; ISSN JAMSEF
Country of Publication:
United States
Language:
English

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