For Prospective Students:

In general, we study how molecules stick (bind) together. Such binding events govern many processes in biology, but they are not well understood at the chemical level. As bioorganic chemists, we use techniques in organic chemistry, such as chemical synthesis and NMR spectroscopy, to probe the structure and reactivity of biological molecules, such as proteins and nucleic acids. We design and characterize model compounds which act like biomolecules but are easier to study. One major goal is to design compounds that can selectively bind to (or “recognize”) specific biomolecules (see Figure 1), thus giving us a way to alter their reactivity. Drugs do this—each recognizes a specific target protein, binds tightly to it, and inhibits its activity. A second major goal is to use model compounds to better understand the natural behavior of biomolecules, such as how multiple weak interactions can add up to a very strong interaction.

 

 

Figure 1. A view of the inside of the binding pocket of the enzyme Human Carbonic Anhydrase II, with a small drug molecule (an arylsulfonamide) tightly bound. The surface of the protein cavity is labeled with the amino acid residues and zinc ion that we believe are important for molecular recognition and catalysis. The structural coordinates were taken from Proc. Natl. Acad. Sci. USA 2002, 99, pp. 1270-1273 and rendered by George Kaufman (Harvard University) using Pov Ray.

Students in the group learn a variety of techniques, even in their first year of college. These include: 1) organic and solid-phase synthesis to make peptides and other small molecules; 2) NMR and circular dichroism spectroscopy, mass spectrometry, and X-ray crystallography to characterize molecular structure; 3) microcalorimetry, stopped-flow spectroscopy, and capillary electrophoresis to measure the thermodynamics and kinetics of binding; 4) UV-visible and fluorescence spectroscopy to study electronic properties; and 5) computational methods for modeling relatively large molecules and complexes. This combination of methods and approaches offers students a breadth of technique and depth of study that is excellent training for future work in a wide range of areas.

For further information and to discuss research opportunities in the group, please contact Dr. Urbach.