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DEPARTMENT PEOPLE GRADUATE STUDIES UNDERGRADUATE STUDIES RESEARCH CONTACT US
  

Xudong Yao

 

Analytical Chemistry and Proteomics

Assistant Professor (b. 1965)

Scientist II, Millennium Pharmaceuticals, 2002-2004

Senior Scientist, GeneProt, 2002
Postdoctoral Associate, University of Maryland, 1999-2002
Ph.D., University of Maryland Baltimore County, 2000
M.S., Nanjing University, 1987

B.S., Nanjing University, 1984

Phone: 860-486-6644
Email : x.yao@uconn.edu

Yao Group Home Page

 

Research

We develop chemical principles and invent new methods for the targeted analysis of complex and dynamic “-ome” samples. A special emphasis is on the novel combination of solution derivatization with gas-phase dissociation of biomolecules, in order to produce small fragment ions with ultra-high specificity and high chemical yield for advanced mass spectrometry. A scaling analysis principle has been proposed for designing the fragment ions and analyzing spectral data, which has led to the development of novel classes of iodine-based chemical labeling reagents.

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.

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.


Other research projects include chemical proteomics of enzymes and mass spectrometry of membrane proteins and biomarkers.

Represenatative Publications:


1. “Cyclophosphoramidate ion as mass defect marker for efficient detection of protein serine phosphorylation,” Y. Shi, B. Bajrami, M. Morton, X. Yao, Analytical Chemsitry, ASAP; Web Release Date: 10-Sep-2008.


2. “Averagine-scaling analysis and fragment ion mass defect labeling in peptide mass spectrometry,” X. Yao, P. Diego, A.A. Ramos, Y. Shi, Analytical Chemsitry, ASAP; Web Release Date: 09-Sep-2008.


3. “Oxygen isotopic substitution of peptidyl phosphates for modification-specific mass spectrometry,” Y. Shi, X. Yao, Analytical Chemistry, 2007, 79, 8454.


4. “Tandem parallel fragmentation of peptides for mass spectrometry,” A.A. Ramos, H. Yang, L.E. Rosen, X. Yao, Analytical Chemistry, 2006, 78, 6391.


5. “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,” M. Heller, H. Mattou, C. Menzel, X. Yao, Journal of American Society for Mass Spectrometry, 2003, 14, 704.


6. “Dissection of proteolytic 18O labeling: endoprotease-catalyzed 16O-to-18O exchange of truncated peptide substrates,” X. Yao, C. Afonso, C. Fenselau, Journal of Proteome Research, 2003, 2, 147.


7. “Proteolytic 18O labeling for comparative proteomics: model studies with two serotypes of adenovirus,” X. Yao, A. Freas, J. Ramirez, P.A. Demirev, C. Fenselau, Analytical Chemistry, 2001, 73, 2836; Top-Ten cited paper in Analytical Chemsitry.


8. “Transition state imbalance in proton transfer from phenyl ring substituted 2-tetralones to acetate ion,” X. Yao, M.A. Gold, R. M. Pollack, Journal of the American Chemical Society, 1999, 121, 6220.


 

      
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