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Synthesis and Mass Spectrometry Analysis of Oligo-peptoids
Published on: February 21, 2018
Sequence-scrambling fragmentation pathways of protonated peptides
Christian Bleiholder1, Sandra Osburn, Todd D Williams
1Department of Molecular Biophysics, Im Neuenheimer Feld 580, German Cancer Research Center, 69120 Heidelberg, Germany.
Journal of the American Chemical Society
|December 6, 2008
Summary
Collision-induced dissociation (CID) of peptide fragments reveals that b ions rapidly cyclize, leading to fragmentation patterns determined by the cyclic isomer. This cyclization-reopening mechanism can cause loss of sequence information during peptide analysis.
Area of Science:
- Analytical Chemistry
- Computational Chemistry
- Biochemistry
Background:
- Understanding peptide fragmentation in mass spectrometry is crucial for sequence determination.
- Collision-induced dissociation (CID) is a common technique for peptide fragmentation.
- The behavior of N-terminal b and a ions during CID can be complex, involving rearrangements.
Purpose of the Study:
- To investigate the gas-phase structures and fragmentation pathways of N-terminal b and a fragments of specific peptides.
- To elucidate the mechanisms of scrambling and rearrangement reactions during CID of b and a ions.
- To determine the influence of cyclization on CID fragmentation patterns.
Main Methods:
- Experimental investigation using collision-induced dissociation (CID).
- Theoretical analysis using molecular mechanics and density functional theory (DFT) calculations.
- Comparison of fragmentation patterns for linear and cyclic peptide isomers.
Main Results:
- Low-energy CID of b(5) fragments from various peptides yielded similar dissociation patterns.
- CID of protonated cyclo-(YAGFL) produced identical fragments and ion abundances as linear b(5) ions, suggesting rapid cyclization.
- Computational results supported a cyclization-reopening mechanism, with protonated cyclo-(YAGFL) being energetically favored over linear isomers.
Conclusions:
- The fragmentation spectra of linear b(5) ions are dominated by their cyclic isomers due to rapid cyclization and facile interconversion.
- This cyclization-reopening mechanism can lead to a complete loss of sequence information during CID.
- CID of a(5) ions involves b-type scrambling and a --> a*-type rearrangements, with cyclization followed by reopening to the linear structure.
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