Current Research

My research group specializes in the development and application of Fourier transform mass spectrometry for solving difficult problems in bioanalytical chemistry. We are exploring new methods for analyzing the structural features of glycosaminoglycans (GAGs), a class of carbohydrates that play a central role in a number of important biological processes, including cellular communication, cell signaling, and regulation of biochemical pathways. Our approach uses electron-aided methods of ion activation (electron detachment dissociation, electron induced dissociation, and electron transfer dissociation) to dissociate GAG oligosaccharides, and to provide detailed data regarding sites of sulfation, acetylation, and uronic acid stereochemistry. We are exploring the use of chemometric analysis (principal component analysis and partial least squares discriminant analysis) for maximizing the amount of analytical information that can be extracted from the highly complex tandem mass spectra produced by electron detachment dissociation of GAGs. We are developing rapid and sensitive methods for measuring changes in the cellular levels of proteins. Our approach is to harvest complex protein mixtures from a cell, enzymatically digest the proteins into peptides, and to identify the peptides by accurate mass measurement using Fourier transform mass spectrometry. This process is aided by a combination of capillary scale separation methods, chemical derivitization methods using compounds synthesized in our laboratory, and isotope labeling. Other recent research projects include the use of advanced computational methods for carrying out multiparticle simulations of ion motion within the FTICR mass analyzer. These simulations give detailed information about ion-ion interactions, and provide insight into the limits of mass accuracy in FTICR mass spectrometry.

Selected Publications

Leach, F. E. ; Riley, N. M. ; Westphall, M. S. ; Coon, J. J. Negative Electron Transfer Dissociation Sequencing of Increasingly Sulfated Glycosaminoglycan Oligosaccharides on an Orbitrap Mass Spectrometer. Journal of The American Society for Mass Spectrometry 2017, 28, 1844 - 1854.
Agyekum, I. ; Zong, C. ; Boons, G. - J. ; I. Amster, J. Single Stage Tandem Mass Spectrometry Assignment of the C-5 Uronic Acid Stereochemistry in Heparan Sulfate Tetrasaccharides using Electron Detachment Dissociation. Journal of The American Society for Mass Spectrometry 2017, 28, 1741 - 1750.
Chen, Y. ; Lin, L. ; Agyekum, I. ; Zhang, X. ; Ange, K. St.; Yu, Y. ; Zhang, F. ; Liu, J. ; I. Amster, J. ; Linhardt, R. J. Structural Analysis of Heparin-Derived 3- O -Sulfated Tetrasaccharides: Antithrombin Binding Site Variants. Journal of Pharmaceutical Sciences 2017, 106, 973 - 981.
Lin, L. ; Liu, X. ; Zhang, F. ; Chi, L. ; I. Amster, J. ; Leach, F. E. ; Xia, Q. ; Linhardt, R. J. Analysis of heparin oligosaccharides by capillary electrophoresis–negative-ion electrospray ionization mass spectrometry. Analytical and Bioanalytical Chemistry 2017, 409, 411 - 420.
Zhao, Y. ; Singh, A. ; Xu, Y. ; Zong, C. ; Zhang, F. ; Boons, G. - J. ; Liu, J. ; Linhardt, R. J. ; Woods, R. J. ; I. Amster, J. Gas-Phase Analysis of the Complex of Fibroblast GrowthFactor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study. Journal of The American Society for Mass Spectrometry 2017, 28, 96 - 109.
Zong, C. ; Huang, R. ; Condac, E. ; Chiu, Y. ; Xiao, W. ; Li, X. ; Lu, W. ; Ishihara, M. ; Wang, S. ; Ramiah, A. ; Stickney, M. ; Azadi, P. ; I. Amster, J. ; Moremen, K. W. ; Wang, L. ; Sharp, J. S. ; Boons, G. - J. Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1. Journal of the American Chemical Society 2016, 138, 13059 - 13067.
Agyekum, I. ; Patel, A. B. ; Zong, C. ; Boons, G. - J. ; I. Amster, J. Assignment of hexuronic acid stereochemistry in synthetic heparan sulfate tetrasaccharides with 2-O-sulfo uronic acids using electron detachment dissociation. International Journal of Mass Spectrometry 2015, 390, 163 - 169.
Kailemia, M. ; Patel, A. ; Johnson, D. ; Li, L. ; Linhardt, R. ; I. Amster, J. Differentiating chondroitin sulfate glycosaminoglycans using collision-induced dissociation; uronic acid cross-ring diagnostic fragments in a single stage of tandem mass spectrometry. European Journal of Mass Spectrometry 2015, 21, 275-285.
Zhao, Y. ; Singh, A. ; Li, L. ; Linhardt, R. J. ; Xu, Y. ; Liu, J. ; Woods, R. J. ; I. Amster, J. Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS). The Analyst 2015.
Singh, A. ; Kett, W. C. ; Severin, I. C. ; Agyekum, I. ; Duan, J. ; I. Amster, J. ; Proudfoot, A. E. I. ; Coombe, D. R. ; Woods, R. J. The Interaction of Heparin Tetrasaccharides with Chemokine CCL5 Is Modulated by Sulfation Pattern and pH. Journal of Biological Chemistry 2015, 290, 15421 - 15436.
Driver, J. A. ; Kharchenko, A. ; Heeren, R. M. A. ; I. Amster, J. Fast image–charge calculations for multi-particle simulations in FT-ICR analyzer cells of arbitrary geometry. International Journal of Mass Spectrometry 2015, 377, 432 - 439.
Awad, H. ; Stoudemayer, M. J. ; Usher, L. ; Amster, I. J. ; Cohen, A. ; Das, U. ; Whittal, R. M. ; Dimmock, J. ; El-Aneed, A. The unexpected formation of [M − H] + species during MALDI and dopant-free APPI MS analysis of novel antineoplastic curcumin analogues. Journal of Mass Spectrometry 2014, 49, 1139 - 1147.
Kailemia, M. J. ; Park, M. ; Kaplan, D. A. ; Venot, A. ; Boons, G. - J. ; Li, L. ; Linhardt, R. J. ; Amster, I. J. High-Field Asymmetric-Waveform Ion Mobility Spectrometry and Electron Detachment Dissociation of Isobaric Mixtures of Glycosaminoglycans. Journal of The American Society for Mass Spectrometry 2014, 25, 258 - 268.
Kailemia, M. J. ; Ruhaak, L. Renee; Lebrilla, C. B. ; Amster, I. J. Oligosaccharide Analysis by Mass Spectrometry: A Review of Recent Developments. Analytical Chemistry 2014, 86, 196 - 212.
Kailemia, M. J. ; Li, L. ; Xu, Y. ; Liu, J. ; Linhardt, R. J. ; Amster, I. J. Structurally informative tandem mass spectrometry of highly sulfated natural and chemo-enzymatically synthesized heparin and heparan sulfate glycosaminoglycans. Molecular & Cellular Proteomics 2013, 12, 979-990.
Leach, F. E. ; Arungundram, S. ; Al-Mafraji, K. ; Venot, A. ; Boons, G. - J. ; Amster, I. J. Electron detachment dissociation of synthetic heparan sulfate glycosaminoglycan tetrasaccharides varying in degree of sulfation and hexuronic acid stereochemistry. International Journal of Mass Spectrometry 2012, 330-332, 152 - 159.
Leach, F. E. ; Ly, M. ; Laremore, T. N. ; Wolff, J. J. ; Perlow, J. ; Linhardt, R. J. ; Amster, I. J. Hexuronic Acid Stereochemistry Determination in Chondroitin Sulfate Glycosaminoglycan Oligosaccharides by Electron Detachment Dissociation. J Am Soc Mass Spectrom 2012, 23, 1488-1497.
Leach, F. E. ; Kharchenko, A. ; Vladimirov, G. ; Aizikov, K. ; O’Connor, P. B. ; Nikolaev, E. ; Heeren, R. M. A. ; Amster, I. J. Analysis of phase dependent frequency shifts in simulated FTMS transients using the filter diagonalization method. Int J Mass Spectrom 2012, 325-327, 19-24.
Kailemia, M. J. ; Li, L. ; Ly, M. ; Linhardt, R. J. ; Amster, I. J. Complete Mass Spectral Characterization of a Synthetic Ultralow-Molecular-Weight Heparin Using Collision-Induced Dissociation. Anal Chem 2012, 84, 5475 - 5478.
Ly, M. ; Leach, F. E. ; Laremore, T. N. ; Toida, T. ; Amster, I. J. ; Linhardt, R. J. The proteoglycan bikunin has a defined sequence. Nature Chemical Biology 2011, 7, 827-833.