Collision-activated dissociation (CAD), the most widely used peptide ion fragmentation technique for peptide sequence analysis by tandem mass spectrometry, works great for small peptides but is problematic for labile posttranslational modifications (PTMs). In the last decade, researchers have developed an alternative, electron capture dissociation (ECD), which involves reacting multiply-protonated peptides with thermal electrons, and provides random cleavage of the peptide backbone while leaving most labile PTMs attached and intact. The drawback: Mixing cations and electrons requires a high magnetic field, only present in Fourier transform ion cyclotron resonance mass spectrometers, which few labs can afford.
Another group has since developed an ion/ion analog of ECD, electron transfer dissociation (ETD), that is compatible with widely used and more affordable RF ion trap mass analyzers. Ion traps' radio frequency (RF) electric fields can confine both cations and anions, but not cations and vastly lighter electrons, so ETD uses specially-chosen anions to act ...
