Radical stability directs electron capture and transfer dissociation of β-amino acids in peptides.
We report on the characteristics of the radical-ion-driven dissociation of a diverse array of β-amino acids incorporated into α-peptides, as probed by tandem electron-capture and electron-transfer dissociation (ECD/ETD) mass spectrometry. The reported results demonstrate a stronger ECD/ETD dependence on the nature of the amino acid side chain for β-amino acids than for their α-form counterparts. In particular, only aromatic (e.g., β-Phe), and to a substantially lower extent, carbonyl-containing (e.g., β-Glu and β-Gln) amino acid side chains, lead to N-Cβ bond cleavage in the corresponding β-amino acids. We conclude that radical stabilization must be provided by the side chain to enable the radical-driven fragmentation from the nearby backbone carbonyl carbon to proceed. In contrast with the cleavage of backbones derived from α-amino acids, ECD of peptides composed mainly of β-amino acids reveals a shift in cleavage priority from the N-Cβ to the Cα-C bond. The incorporation of CH2 groups into the peptide backbone may thus drastically influence the backbone charge solvation preference. The characteristics of radical-driven β-amino acid dissociation described herein are of particular importance to methods development, applications in peptide sequencing, and peptide and protein modification (e.g., deamidation and isomerization) analysis in life science research.
Biomolecular Mass Spectrometry Laboratory, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne (Switzerland), Fax: (+41) 21-693-9700.
Hisham
H
Ben Hamidane
Aleksey
A
Vorobyev
Maud
M
Larregola
Aneta
A
Lukaszuk
Dirk
D
Tourwé
Solange
S
Lavielle
Philippe
P
Karoyan
Yury O
YO
Tsybin
D000596:Amino Acids / Q000737:chemistry*; D004579:Electron Transport; D004583:Electrons; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D010455:Peptides
amino acids; electron capture; electron transfer; mass spectrometry; radical ions; radical stability