People

Christian Bleiholder

Tel: 805-893-2673

E-mail: cbleiholder@chem.ucsb.edu

I obtained my M.Sc. in 2004 at the University of Heidelberg in the laboratory of Prof. R. Gleiter (Institute of Organic Chemistry) and my Ph.D. in 2007 at the German Cancer Research Center (Profs. R. Gleiter and S. Suhai, Department of Molecular Biophysics). Subsequently, I joined the laboratory of Prof. Bowers at UCSB in 2008 to pursue postdoctoral studies in ion mobility spectrometry-mass spectrometry (IMS-MS). My awards include an Alexander-von-Humboldt Fellowship (2007) and a Postdoctoral Research Award of the American Chemical Society (2011).

My research in the Bowers group focuses on the formation of fibrillar protein assemblies implicated in amyloid diseases, including Alzheimer’s and type 2 diabetes. Understanding the fundamental principles that relate aggregation, morphology and biochemistry of soluble peptide aggregates is central to developing diagnostic and therapeutic strategies for amyloid diseases. So far, these processes have resisted detailed characterization due to the transient and dynamic nature of early peptide oligomers. Our recently published results (Nature Chemistry, 2011) show transitions of early, soluble peptide oligomers from a globular to a fibrillar conformation, demonstrating that IMS-MS is capable of elucidating the structural processes involved during the onset of amyloid formation.

The theory of ion mobility is another aspect of my research with Prof. Bowers. One of the crucial unsolved problems in ion mobility studies is the efficient and accurate determination of collision cross sections of macromolecular species from model structures, especially for biological macromolecules. Good algorithms exist for small systems but once the molecule reaches several thousand atoms the projection methods become unacceptably inaccurate and the trajectory method becomes unacceptably time consuming. This, and larger, are size regimes that many are now working in. Recently (IJMS, in press), we presented a modified version of the projection method that retains much of is computational efficiency while adding the accuracy of the trajectory method. The software implementation will be made publicly available.

Previous work involved quantum mechanical modeling of transition metal complexes, intermolecular interactions, as well as the gas-phase chemistry of protonated peptides.

Publications

• A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (III). Application to supramolecular coordination-driven assemblies.
  S. E. Anderson, C. Bleiholder, E. R. Brocker, P. J. Stang, M. T. Bowers
  Submitted.
• Dimerization of chirally mutated Enkephalin neurotransmitters: Implications for peptide and protein aggregation mechanisms.
  C. Bleiholder, N. F. Dupuis, M. Murray Gessel, M. T. Bowers
  Submitted.
• On the relationship between conformation and opioid activity of chirally substituted Leu-Enkephalin peptides: Gly(2) in YGGFL is a surrogate for D-Ala(2).
  C. Bleiholder, M. T. Bowers
  Submitted.
• A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (II). Model parameterization and definition of empirical shape factors for proteins.
  C. Bleiholder, S. Contreras, T. D. Do, M. T. Bowers
  Submitted.
• A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (I). Method.
  C. Bleiholder, T. Wyttenbach, M. T. Bowers
  Int. J. Mass Spectrom. 2011, 308, 1-10.
• Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro-Ala (Xxx =Ala, Ser, Leu, Val, Phe, and Trp).
  C. Bleiholder, S. Suhai, A. G. Harrison, B. Paizs
  J. Am. Soc. Mass Spectrom. 2011, 22, 1032-1039.
• Ion mobility–mass spectrometry reveals a conformational conversion from random assembly to beta-sheet in amyloid fibril formation.
  C. Bleiholder, N. F. Dupuis, T. Wyttenbach, M. T. Bowers
  Nature Chem. 2011, 3, 172-177.
• Does the structure of biopolymers resemble that in solution?
  T. Wyttenbach, C. Bleiholder, C. Wu, M. Grabenauer, M. T. Bowers
  Proceedings of the 58th ASMS Conference on Mass Spectrometry and Allied Topics, Salt Lake City, UT 2010, 006.
• Ion mobility spectrometry/mass spectrometry reveals conformational conversion from random assembly to beta-sheet-rich oligomers in amyloid fibril forming peptides.
  C. Bleiholder, N. F. Dupuis, T. Wyttenbach, M. T. Bowers
  Proceedings of the 58th ASMS Conference on Mass Spectrometry and Allied Topics, Salt Lake City, UT 2010, 044.
• Competing gas-phase fragmentation pathways of asparagine-, glutamine-, and lysine-containing protonated dipeptides.
  C. Bleiholder, B. Paizs
  Theo. Chem. Acc. 2010, 125, 387-396.
• Intramolecular nonbonded interactions between divalent selenium centers with donor and acceptor substituents.
  A. Lari, C. Bleiholder, F. Rominger, R. Gleiter
  Eur. J. Org. Chem. 2009, 17, 2765-2774.
• α-Metallocenylmethylium ions and their isoelectronic congeners - a comparison based on DFT calculations.
  C. Bleiholder, F. Rominger, R. Gleiter
  Organometallics 2009, 28, 1014-1017.
• Peptide chirality and its effects on folding and aggregation.
  M. T. Bowers, C. Bleiholder, N. Dupuis
  Abstr. Paper Am. Chem. Soc. Natl. Meet. 2009, 238, 323-ANYL.
• Sequence scrambling fragmentation pathways of protonated peptides.
  C. Bleiholder, S. Osburn, T. Williams, S. Suhai, M. Van Stipdonk, A. Harrison, B. Paizs
  J. Am. Chem. Soc. 2008, 130, 17774–17789.
• α-Metallocenylmethyliumions of d6 to d9 metals. Structural considerations.
  R. Gleiter, C. Bleiholder, F. Rominger
  Organometallics 2007, 26, 4850-4859.
• Unimolecular chemistry of metal ion-coordinated α-dipeptide radicals.
  F. Pingitore, C. Bleiholder, B. Paizs, C. Wesdemiotis
  Int. J. Mass Spectrom. 2007, 265, 251-260.
• Theoretical investigations on heteronuclear chalcogen-chalcogen interactions: On the nature of weak bonds between chalcogen centers.
  C. Bleiholder, R. Gleiter, D. B. Werz, H. Köppel
  Inorg. Chem. 2007, 46, 2249-2260.
• Sequence scrambling pathways of protonated peptides upon CID.
  C. Bleiholder, T. Cooper, J. Groves, A. B. Young, S. Suhai, M. Van Stipdonk, A. G. Harrison, B. Paizs
  Proceedings of the 55th ASMS Conference on Mass Spectrometry and Allied Topics, Indianapolis, IN 2007,081.
• Transannular interactions in mixed superphanes with one thiophene and one CpCo-stabilized cyclobutadiene ring: Syntheses, structures, and electrochemistry.
  S. Gath, R. Gleiter, F. Rominger, C. Bleiholder
  Organometallics 2007, 26, 644–650.
• Scrambling of sequence information in collision-induced dissociation of peptides.
  A. G. Harrison, A. B. Young, C. Bleiholder, S. Suhai, B. Paizs
  J. Am. Chem. Soc. 2006, 128, 10364-10365.
• Strong distortions in hexacarbonyldicobalt complexes by push-pull effects.
  D. B. Werz, C. Bleiholder, R. Gleiter, F. Rominger
  J. Organomet. Chem. 2006, 691, 3943-3947.
• Dissociation pathways of singly charged dilithiated peptides.
  C. Wesdemiotis, P. Wang, A. Leigh, M. J. Polce, C. Bleiholder, B. Paizs
  Proceedings of the 54th ASMS Conference on Mass Spectrometry and Allied Topics, Seattle, WA, USA, May 28 – June 1, 2006, p. 282
• Improving the reliability of protein identification using peptide mass fingerprinting by probability based scoring of amino acid modifications.
  C. Bleiholder, S. Fiedler, B. Paizs, M. Schnölzer
  Proceedings of the 54th ASMS Conference on Mass Spectrometry and Allied Topics, Seattle, WA, USA, May 28 – June 1, 2006, p. 581
• Fragmentation mechanisms of protonated peptides.
  C. Bleiholder, S. Suhai, B. Paizs
  Proceedings of the 54th ASMS Conference on Mass Spectrometry and Allied Topics, Seattle, WA, USA, May 28 – June 1, 2006, p. 1875
• Effective temperatures and the mobile proton in activated ions, evaluated by thermal extrapolation and by ab initio calculations.
  M. Mautner, A. Somogyi, C. Bleiholder, B. Paizs
  Proceedings of the 54th ASMS Conference on Mass Spectrometry and Allied Topics, Seattle, WA, USA, May 28 – June 1, 2006, p. 2319
• Revising the proton affinity scale of the naturally occuring α-amino acids.
  C. Bleiholder, S. Suhai, B. Paizs
  J. Am. Soc. Mass Spectrom. 2006, 17, 1275-1281.
• Structural characterization of peptides via tandem mass spectrometry of their dilithiated monocations.
  P. Wang, M. J. Polce, C. Bleiholder, B. Paizs, C. Wesdemiotis
  Int. J. Mass Spectrom. 2006, 249, 45-59.
• Theoretical investigations on chalcogen-chalcogen-interactions: What makes these nonbonded interactions bonding?
  C. Bleiholder, D. B. Werz, H. Köppel, R. Gleiter
  J. Am. Chem. Soc. 2006, 128, 2666-2674
• Coordination chemistry of a new rigid, hexadentate bispidine-based bis(amine)tetrakis(pyridine) ligand.
  C. Bleiholder, H. Borzel, P. Comba, R. Ferrari, M. Heydt, M. Kerscher, S. Kuwata, G. Laurenczy, G. A. Lawrance, A. Lienke, B. Martin, M. Merz, B. Nuber, H. Pritzkow
  Inorg. Chem. 2005, 44, 8145-8155