Thomas Hellman Morton
Professor of Chemistry
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Physical Biochemistry
Ph.D., California Institute of Technology, 1973
VOICE: 951-827-4735 |
Covalent modification (also known as crosslinking) of membrane proteins is an important tool in biological chemistry. It identifies the target site so that cell surface receptors can be characterized and their binding sites sequenced. One method is called affinity labeling, where the natural ligand (or a mimic) is converted into a reactive species that becomes irreversibly attached. Our objective is to invent specific affinity labels and to devise techniques to pinpoint where they become fixed. The Morton group has developed a set of two-step approaches. Two-step covalent modification takes a small molecule that binds reversibly (which we call the blocker) and reacts its bound form with a second reagent (called the fixer) to put a permanent tag onto the binding site. Two-step affinity chromagraphy (which can be used in conjunction with two-step covalent modification) tethers modified proteins to a surface with an extender arm containing a cleavable linker. Thus the modified protein can be specifically eluted from the surface for purification. These two-step approaches have been reduced to practice using soluble proteins and are now being implemented on cell surfaces, so that a variety of techniques (both radiolabeling and mass spectrometry) can be used to identify the binding sites.
SELECTED PUBLICATIONS
Audier, H.E., Berthomieu, D., Leblanc, D. and Morton, T.H. Multiple protonation sites in Aryl ethers. International Journal of Mass Spectrometry and Ion Processes 175:133-147 (1998).
Nguyen, V., Bennett, J.S. and Morton, T.H. Bridging versus hydride shift in gaseous cafrons: Hydroxy as a vicinal substituent. J. Am. Chem. Soc. 119:8342-8349 (1997).
Illies, A.J. and Morton, T.H. Strong hydrogen bonding in the gas phase. International Journal of Mass Spectrometry and Ion Processes 167: 431-445 (1997).
Taphanel, M.-H., Morizur, J.P., Leblanc, D. Borchardt, D. and Morton, T.H. Stereochemical analysis of monodeuterated isomers by GC/MS/MS. Analytical Chemistry 69:4191-4196 (1997).
Audier, H.E., Bennett, J.S., Kelcher, M.G. and Morton, T.H. Chiral substitution with isotopic hydrogen: mass spectrometry and the diastereomer problem. In, The Synthesis and Applications of Isotopes and Isotopically Labelled Compounds, Wiley-Interscience, pp. 482-488 (1995).
Song, K., van Eijk, A., Shaler, T.A. and Morton, T.H. Fragment ion formation in resonance-enhanced multiphoton ionization (rempi) of n-propyl ether in a supersonic jet. J. Am. Chem. Soc. 116:4455-4460 (1994).
McAdoo, D.J. and Morton, T.H. Gas phase analogues of cage effects. Accounts of Chemical Research 26:295-302 (1993).
Lin, W.-C. and Morton, T.H. Two-step affinity chromatography. Model systems and an example using biotin-avidin binding and a fluoridolyzable linker. J. Org. Chem. 56:6850-6856 (1991).