Contact Information
email: skent@uchicago.edu
phone: 2-4912
office: CIS W204

Technical Expertise
  · chemical protein synthesis
  · enzyme catalysis
  · protein molecular structure
  · peptide mimetics
  · polymer supported organic synthesis

Special Equipment & Techniques
  · electrospray mass spectrometry

Research Description
We apply the tools of chemistry to elucidate the molecular basis of the biological functions of proteins. Ultimately we want to be able to design and build protein molecules with pre-determined, controlled properties. This is a scientific problem of great timeliness with the impending completion of the genome projects, which impact broadly across the natural sciences.

In the post-genome era it will be imperative to understand the principles that govern the numerous and diverse activities of proteins in the biological world. These principles can best be elucidated by combining a number of scientific disciplines. To that end, we have established general synthetic access to the world of proteins. This enables us to focus the most advanced physical and chemical techniques in conjunction with all the tools of molecular biology to elucidate the molecular basis of the biochemical and biological actions of the protein molecule.

The emphasis in our research program is on collaborative science. This creates unique opportunities for people drawn to the application of chemistry to biological systems. Thus, techniques such as nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) spectroscopy can be applied to protein systems that have been labeled in a non-perturbing fashion with probe nuclei to act as local reporter groups. This enables the fruitful application of these powerful methods to complex protein systems. Synthetic organic and peptidomimetic chemistry can also be used to systematically dissect the molecular basis of enzyme activity by varying the covalent structure of a protein in a completely general yet controlled fashion, and correlating these precise changes with effects on protein function.

Our areas of current interest include the elucidation of the detailed mechanism of catalysis in systems such as the HIV-1 Protease, and the enzymes b-Secretase and g-Secretase, all three of which are aspartyl proteinases of great importance in biomedical research. Of particular interest are the precise electronic nature of chemical catalysis in these enzymes and the dynamic structural events that occur in the course of catalysis. Other applications of the combined chemistry and protein biochemical approaches include fundamental studies of protein folding, exploration of the properties of 'mirror image' protein molecules and the construction of unique topological analogues of proteins. By combining synthetic chemistry, physical chemistry, and biology we will develop a new understanding of how proteins carry out their roles as the 'molecular machines' of the biological world.