Carlito B. Lebrilla

Professor

Email: lebrilla@chem.ucdavis.edu

Analytical Chemistry

B.S., University of California, Irvine, 1981. Ph.D., University of California, Berkeley, 1985. Alexander von Humboldt postdoctoral Fellow, Technical University, Berlin, 1985-86. NATO-NSF Postdoctoral Fellow, Technical University, Berlin, 1986-87. UC President's Fellow, UC Irvine, 1988-89. Appointed to faculty, UC Davis, 1989-.

Research Interests

Mass spectrometry, Bio-analytical chemistry, Gas-phase chiral analysis.

The group currently has two major instruments a novel dual chamber external source Fourier transform mass spectrometry (FTMS) instrument with matrix-assisted laser desorption/ionization, electrospray, fast atom bombardment, and electron impact ionization sources and a fully dedicated MALDI/FTMS instrument. Both instruments are state-of-the-art and equipped with 5 Tesla superconducting magnets. Students in the group acquire a well-rounded education in mass spectrometry including instrument development and fabrication, methods development, biochemistry, ion/molecule chemistry, and ion physics.

DEVELOPMENT OF NEW MASS SPECTROMETRIC TECHNIQUES

A major component of the group's research, besides the application of mass spectrometry, is in developing new mass spectrometric techniques. We built the dual chamber instrument including all the ionization sources, the ion optics, and the vacuum chamber. This instrument has become a prototype for an inexpensive mass spectrometer with enhanced capabilities. It has now been duplicated by several instrument manufacturers. Improvements to matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) in terms of sensitivity and ionization efficiencies are continuing projects in the group. These techniques are useful for ionizing a host of different compounds. We are also developing methods to couple both ionization techniques to separations techniques to further enhance the capabilities of the instrument. We are currently performing studies in collaboration with the Microfabrication Facility in U.C. Davis to build inexpensive and disposable analytical devices for mass spectrometry.

MASS SPECTROMETRIC DETERMINATION OF OLIGOSACCHARIDES

Oligosaccharides play a key role in important cellular processes such as recognition, adhesion and division. These compounds however have specific problems when analyzed bymass spectrometry. The problems include the large number of stereoisomers and possible linkage combinations, and the lack of fragmentation products. We are developing a general method to overcome many of the difficulties. Such a method must include an understanding of the compound's fragmentation behavior during ionization, and its affinities for different binding cations. For example, we find that certain cations such as K+ and Na+ stabilize the parent ion better than other cations such as H+. A better control of the fragmentation yield will allow us to obtain mass spectra that contain only molecular or pseudomolecular ions. Our analytical efforts in oligosaccharides are focused on two specific problems: the analysis of oligosaccharides in the egg-jelly of the South African toad Xenopus laevis and oligosaccharides found in endothelial cells. The first deals with the process of fertilization and the second with cancer. These projects require the development of sensitive methods to analyze complex mixtures composed of dozens of oligosaccharides. We are pioneering the structural catalog approach to analyze these complex libraries of oligosaccharides.

ION/MOLECULE CHEMISTRY OF GAS-PHASE INCLUSION COMPLEXES

Chiral recognition using mass spectrometry is an idea that is also being developed for analytical purposes. It is commonly believed that mass spectrometry can not be used to differentiate chirality. However, two very important gas-phase reactions were recently discovered in the group that show large specificity between enantiomers of small alkyl amines and amino acids. The nature of these reactions and the chiral specificity are still unknown and are being pursued actively. This study will also attempt to answer the question of the existence gas-phase inclusion complexes. Are the solution-phase structures of cyclodextrin complexes retained during ionization so that gas-phase inclusion complexes are formed. This question has significant importance in drug design and drug delivery.

Publications

Ramirez, J., F. He, and C.B. Lebrilla. 1998. Gas-phase chiral differentiation of amino acid guests in cyclodextrin hosts. J. Am. Chem. Soc., in press.

Cancilla, M.T., S.G. Penn, and C.B. Lebrilla. 1998. Alkaline degradation of oligosaccharides coupled with matrix-assisted laser desorption /ionization - Fourier transform mass spectrometry: A new method for sequencing oligosaccharides. Anal. Chem., 70, 663-672.

Tseng, K., L.L. Lindsay, S.G. Penn, J.L. Hedrick, and C.B. Lebrilla. 1997. Characterization of neutral oligosaccharide-alditols from xenopus laevis jelly coats by matrix assisted laser desorption Fourier transform mass spectrometry. Anal. Biochem., 250, 18-28.

Green, M.K. and C.B. Lebrilla. 1997. Ion-molecular reactions as probes of gas-phase structures of peptides and proteins. Mass Spectrom. Rev., 16, 53-71.

Penn, S.G., F. He, M.K. Green, and C.B. Lebrilla. 1997. The use of heated capillary dissociation and collision-induced dissociation to determine the strength of noncovalent bonding interactions in gas-phase peptide-cyclodextrin complexes. J. Am. Soc. Mass Spectrom., 8, 244-252.

Camara, E., M.K. Green, S.G. Penn, and C.B. Lebrilla. 1996. Chiral recognition is observed in the deprotonation reaction of cytochrome c by (2R)- and (2S)-butylamine. J. Am. Chem. Soc., 118, 8751-8752.

Carroll, J.A. S.G. Penn, S.T. Fannin, J. Wu, Cancilla, M.T., and C.B. Lebrilla. 1996. A dual vacuum chamber Fourier transform mass spectrometer with rapidly interchangeable LSIMS, MALDI, and ESI sources: Initial results with LSIMS and MALDI. Anal. Chem., 68, 1798-1804.