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

  • David J. Foreman
  • John T. Lawler
  • Mary L. Niedrauer
  • Matthew A. Hostetler
  • Scott A. McLuckeyEmail author
Focus: Honoring Helmut Schwarzʻs Election to the National Academy of Sciences: Research Article

Abstract

A strategy to sequence lysine-containing cyclic peptides by MSn 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 HAuNH3 from [M + Au]+. While some competitive processes are observed, the site of ring opening can be pinpointed to the lysine residue upon MS4 enabling the unambiguous sequencing of cyclic peptides.

Keywords

Gold cationization Cyclic peptides Ion/ion reactions Sunflower trypsin inhibitor 

Notes

Acknowledgements

This work was supported by the National Institutes of Health (NIH) under Grant GM R37-45372. Vanessa M. Kung of the Gellman Lab at the University of Wisconsin is acknowledged for synthesis of the β-Loop cyclic peptide and Samuel H. Gellman is acknowledged for providing the peptide to our laboratory.

Supplementary material

13361_2019_2247_MOESM1_ESM.docx (1.4 mb)
ESM 1 (DOCX 1385 kb)

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© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Department of ChemistryPurdue UniversityWest LafayetteUSA

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