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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
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
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
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
how multiple weak
interactions can add up to a very strong interaction.
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.
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
further information and to discuss research opportunities in the
group, please contact Dr.