The proposed research is intended to satisfy the demands of the high priority topic Comprehensive Biomolecular Mass Spectrometry (03-DA-103*) for the funding opportunity RFA-OD-09-003.
We aim to develop a new approach for identifying glycan isomer structures. These structures have recently been implicated as possible markers for characterizing disease states. We propose to develop an IMS-trap with photodissociation capabilities. Recent developments in ion mobility spectrometry (IMS) include the development of the high-resolution approach termed overtone mobility spectrometry (OMS). OMS offers tremendous advantages in its ability to isolate ions of specific mobilities from continuous ionization sources such as electrospray ionization (ESI). Here we propose to couple this high-resolution isolation technique with a new, high-efficiency photofragmentation method in order to enhance identification of glycan isomers. The proposed instrument consists of an OMS drift tube that is coupled to a LTQ (ThermoScientific) mass spectrometer. The mass spectrometer is outfitted with a F2 laser that can be used to induce precursor ion fragmentation. The combination of high-energy fragmentation (from UV excitation) with low-energy fragmentation (from CID) provides a powerful means of identifying glycan isomers. The synergy of the two techniques offers an effective method for identifying species in very complicated mixtures. The method described in the proposal is ideally suited for the identification of serum glycans as many of these exist as a variety of isomeric species. Considering the diverse role of carbohydrates in biological processes, the success of the proposed research could have wide impact on human health ranging from biomarker discovery efforts to studies of aging at the molecular level.
A novel hybrid ion mobility/linear ion trap mass spectrometer having unique capability for characterizing the structures of complex biomolecules will be constructed. It will then be applied to the analysis of prototype glycan isomers and glycans derived from the blood serum of cancer patients.
| Shi, Liuqing; Holliday, Alison E; Glover, Matthew S et al. (2016) Ion Mobility-Mass Spectrometry Reveals the Energetics of Intermediates that Guide Polyproline Folding. J Am Soc Mass Spectrom 27:22-30 |
| Pierson, Nicholas A; Clemmer, David E (2015) An IMS-IMS threshold method for semi-quantitative determination of activation barriers: Interconversion of proline cis?trans forms in triply protonated bradykinin. Int J Mass Spectrom 377:646-654 |
| Zhu, Feifei; Glover, Matthew S; Shi, Huilin et al. (2015) Populations of metal-glycan structures influence MS fragmentation patterns. J Am Soc Mass Spectrom 26:25-35 |
| Lee, Sunyoung; Glover, Matthew S; Reilly, James P et al. (2015) Photosynthesis of a combinatorial peptide library in the gas phase. Anal Chem 87:9384-8 |
| Ewing, Michael A; Conant, Christopher R P; Zucker, Steven M et al. (2015) Selected overtone mobility spectrometry. Anal Chem 87:5132-8 |
| Masson, Antoine; Kamrath, Michael Z; Perez, Marta A S et al. (2015) Infrared Spectroscopy of Mobility-Selected H+-Gly-Pro-Gly-Gly (GPGG). J Am Soc Mass Spectrom 26:1444-54 |
| Shi, Huilin; Clemmer, David E (2014) Evidence for two new solution states of ubiquitin by IMS-MS analysis. J Phys Chem B 118:3498-506 |
| Wyttenbach, Thomas; Pierson, Nicholas A; Clemmer, David E et al. (2014) Ion mobility analysis of molecular dynamics. Annu Rev Phys Chem 65:175-96 |
| Shi, Huilin; Atlasevich, Natalya; Merenbloom, Samuel I et al. (2014) Solution dependence of the collisional activation of ubiquitin [M + 7H](7+) ions. J Am Soc Mass Spectrom 25:2000-8 |
| Pierson, Nicholas A; Chen, Liuxi; Russell, David H et al. (2013) Cis-trans isomerizations of proline residues are key to bradykinin conformations. J Am Chem Soc 135:3186-92 |
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