faculty

Dow Corning Assistant Professor of Chemistry
Ph.D., Uppsala University, Sweden

Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for
Biomolecular Identification and Structural Characterization

Phone: (734) 615-0570
E-mail: kicki@umich.edu

Research Group

Our research focuses on applying state-of-the-art mass spectrometric techniques to the following areas:
1) identification and characterization of protein posttranslational modifications;
2) mapping macromolecular contact surfaces; and
3) exploration of the gas-phase fragmentation behavior of various biomolecules following ion-electron interactions.

A major goal is to excel in both analytical technique development and biologically relevant problem solving. Electron Capture dissociation (ECD) is a recently developed fragmentation technique for gas-phase peptide and protein ions. ECD can cleave backbone bonds with retention of weakly-bound posttranslational modifications, thereby allowing their localization while simultaneously resulting in amino acid sequence information. By contrast, the main dissociation pathways in slow-heating techniques, such as infrared multiphoton dissociation (IRMPD), are loss of and cleavage within modifications. IRMPD can therefore identify the presence of modifications, and provide complementary structural information. We incorporate ECD and IRMPD into the field of proteomics to specifically target modified proteins at low (fmol) levels.

Solution-phase hydrogen/deuterium exchange in combination with mass spectrometric detection of proteolytic peptides is a valuable tool for characterization of protein-protein interactions. The exchange rates of amide hydrogens at contact surfaces generally slow down several orders of magnitude compared to hydrogens accessible to the solvent. We utilize the ultrahigh resolution (m/Delta m_FWHM of several million) and ppm mass accuracy of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to improve peptide assignment, protein sequence coverage, and mass increase measurements. We also apply this technology to characterize protein-nucleic acid and protein-carbohydrate interactions, and explore the possibility of employing ECD to increase structural resolution.

Finally, we are interested in extending the radical ion chemistry of ECD and other techniques based on ion-electron interactions to structural characterization of a larger variety of biological molecules, such as oligonucleotides and oligosaccharides. Fragmentation patterns of both positive and negative ions are investigated, and should provide insights for a deeper understanding of these processes.

AWARDS

• National Science Foundation Career Award (2005)
• Eli Lilly Analytical Chemistry Award (2005)
• American Society for Mass Spectrometry Research Award (2005)
• Elisabeth Caroline Crosby Research Award (2004)
• 2004 Searle Scholar Award

REPRESENTATIVE PUBLICATIONS

1. HK Kweon, K Hakansson "Selective Zirconium Dioxide-Based Enrichment of Phosphorylated Peptides for Mass Spectrometric Analysis". Anal. Chem. 2006, 78, 1743 (accelerated article). 
2. JT Adamson, K Hakansson "Infrared Multiphoton Dissociation and Electron Capture Dissociation of High Mannose-Type Glycopeptides". J. Proteome Res. 2006, 5, 493.
3. HK Kweon, K Hakansson "Site-Specific Amide Hydrogen Exchange in Melittin Probed by Electron Capture Dissociation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry". Analyst 2006, 131, 275.
4. J Yang, J Mo, JT Adamson, K Hakansson. "Characterization of Oligodeoxynucleotides by Electron Detachment Dissociation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry". Anal. Chem. 2005, 77, 1876
5. KN Schultz, K Hakansson. "Rapid Electron Capture Dissociation of Mass-Selectively Accumulated Oligonucleotide Dications". Int. J. Mass Spectrom., 2004, 234, 123.