Characterization of permethylated β-cyclodextrin-peptide noncovalently bound complexes using electron capture dissociation mass spectrometry (ECD MS)

Abstract

Electron capture dissociation mass spectrometry (ECD MS) was carried out for a number of β-permethylated cyclodextrin (CD)-peptide noncovalent complexes in a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Examined peptides included Angiotensin II (DRVYIHPF), Substance P (RPKPQQFFGLM), and Bradykinin (RPPGFSPFR) and its analogs (PPGFSPFR and RPPGFSPF). ECD MS for doubly protonated complexes [M:CD+2H] 2+ mainly yielded cleavage of the backbones of the constituent peptide with little disassembly of a peptide and β-CD. Analysis of ECD MS fragments indicated that a protonated basic amino-acid residue or N-terminal amino group interacted more favorably with β-CD than did aromatic group-containing amino-acid residues (inclusion complex). In contrast to the formation of inclusion CD complexes in solution, we observed no specific evidence from our ECD MS mass spectra to support the generation of phenyl inclusion complexes in the gas phase. For gas-phase peptides, we suggest that ion–dipole interaction is the main driving force for the formation of noncovalent β-CD complexes rather than phenyl inclusion interactions.