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Averagine-scaling
analysis and fragment ion mass defect labeling
Averagine-scaling analysis and fragment
ion mass defect labeling. The combination of novel averagine-scaling
analysis, or ASA, with unique fragment ion mass defect
labeling, or FIMDL, promises a profound impact on peptide
tandem mass spectrometry, by effectively using the broad
and unoccupied mass spaces in the low m/z region of
mass spectra. ASA guides the design and selection of
chemical reagents for generating peptide fragment ions
with FIMDL groups, and reveals that iodine-containing
reagents have the highest FIMDL efficiency. These reagents
have been demonstrated, for the first time, to shift
the mass defect of peptide fragment ions. ASA also makes
possible the convenient and highly efficient reduction
of the data complexity of peptide tandem mass spectra,
which allows the highly specific detection of fragment
ions with increased mass defects (see figure). Current
work in this project involves (1) application of ASA
to various types of ions including phosphoryl ions,
(2) design, synthesis and development of new iodine-containing
reagents, and (3) application of the ASA and FIMDL principles
to study proteins and proteomes related to human disease
such as cystic fibrosis. |
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Bio-inspired
phosphoryl ions
Bio-inspired phosphoryl ions. Chemical
modification converts peptidyl phosphates to the corresponding
phosphoramidates that are stable in solution, and upon
gas phase collision can universally generate a novel
positive phosphoryl ion, the CyPAA ion; it is the protonated
form of 1,4 dihydro 2 hydroxy 2 oxobenzo[3,1,2]oxazaphosphorine
(see scheme). The sufficient mass defect, as predicted
by ASA and validated by experiments, and the positive
nature of the CyPAA ion allow highly efficient detection
of phosphopeptides in complex mixtures. The unique potential
of the ion as a marker for analyzing targeted phosphopeptides
in mixtures is important to pathway phosphoproteome
analysis of cellular systems, and is being investigated.
The activity change of pathway phosphoproteomes is associated
with human disease as well as the fate of human embryonic
stem cells.
Several collaborative projects involve
biological mass spectrometry and proteomics.
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Represenatative Publications:
1. Bekim Bajrami, Yu Shi, Pascal Lapierre, Xudong Yao
“Shifting Unoccupied Spectral Space in Mass Spectrum
of Peptide Fragment Ions,” Journal of American
Society for Mass Spectrometry, 2009, in press.
2. Yu Shi, Bekim Bajrami and Xudong Yao “Passive
and Active Fragment Ion Mass Defect Labeling: Distinct
Proteomics Potential of Iodine-Based Reagents,”
Analytical Chemistry, ASAP, 2009.
3. Catherine Fenselau, Xudong Yao “18O2-Labeling
in quantitative proteomic strategies: a status report,”
Journal of Proteome Research, 2009, 8, 2140.
4. Xudong Yao, Pamela Diego, Alexis A. Ramos, and Yu
Shi “Averagine-Scaling Analysis of Fragment Ions
with Increased Mass Defect in Peptide Mass Spectrometry,”
Analytical Chemistry, 2008, 80, 7383.
5. Yu Shi, Bekim Bajrami, Martha Morton, Xudong Yao
“Cyclophosphoramidate Ion as Mass Defect Marker
for Efficient Detection of Protein Serine Phosphorylation,”
Analytical Chemistry, 2008, 80, 7614.
6. Yu Shi, Xudong Yao “Oxygen Isotopic Substitution
of Peptidyl Phosphates for Modification-Specific Mass
Spectrometry” Analytical Chemistry, 2007, 79,
8454.
7. Alexis Ramos, Hua Yang, Lauren Rosen, Xudong Yao
“Tandem parallel fragmentation of peptides for
mass spectrometry” Analytical Chemistry, 2006,
78, 6391.
8. Manfred Heller, Hassan Mattou, Christoph Menzel,
Xudong Yao “Trypsin catalyzed 16O-to-18O exchange
for comparative proteomics: comparison on tandem mass
spectrometry using MALDI-TOF, ESI-QqTOF and ESI-ion
trap mass spectrometers,” Journal of American
Society for Mass Spectrometry, 2003, 14(7), 704.
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