Ultra-Accurate Correlation Between Precursor and Fragment Ions in Two-lDimensional Mass Spectrometry: Acetylated vs. Trimethylated Histone Peptides

Two-dimensional mass spectrometry (2D MS) is a method
for tandem
mass spectrometry in which precursor and fragment ions are correlated
by manipulating ion radii rather than by ion isolation. A 2D mass
spectrum contains the fragmentation patterns of all analytes in a
sample, acquired in parallel. We report ultrahigh-resolution narrowband
2D mass spectra of a mixture of two histone peptides with the same
sequence, one of which carries an acetylation and the other a trimethylation
(m/z 0.006 difference). We reduced
the distance between data points in the precursor ion dimension and
compared the accuracy of the precursor-fragment correlation with the
resolving power. We manage to perform label-free quantification on
the histone peptide mixture and show that precursor and fragment ions
can be accurately correlated even though the precursor ions are not
resolved. Finally, we show that increasing the resolution of a 2D
mass spectrum in the precursor ion dimension too far can lead to a
decline in the signal-to-noise ratio.