Christopher Seto
Associate Professor:
Chemistry
Phone: +1 401 863 3587
christopher_seto@brown.edu
Our research interests are aimed toward investigating and manipulating the noncovalent interactions that govern molecular recognition in biological systems. We are studying interactions between proteins and their ligands, between proteins and DNA, and the noncovalent interactions that dictate protein secondary and tertiary structure. These projects utilize traditional tools of organic chemistry such as synthesis and spectroscopic evaluation of molecular structure and conformation, and also employ a variety of more biological techniques such as electrophoresis, enzymology, and protein isolation and purification.
Biography
Education
University of Chicago
B.S. in Chemistry with General Honors: 1982 - 1986
Research Advisor: Professor Philip E. Eaton
Harvard University
M.A. in Organic Chemistry: 1986 - 1988
Ph.D. in Organic Chemistry: 1988 - 1992
Research Advisor: Professor George M. Whitesides
Dissertation Topic: Design, synthesis, and characterization of hydrogen-bonded supramolecular aggregates based on the cyanuric acid·melamine lattice.
Professional Appointments
University of California, Berkeley
Postdoctoral Fellow: 1992 - 1994
Research Advisor: Professor Paul A. Bartlett
Brown University
Assistant Professor of Chemistry: July 1994 – July 2000
Associate Professor of Chemistry: July 2000 - Present
Interests
The diversity of our publications this year demonstrates that all aspects of my research program are moving ahead. One of our papers describes our development of inhibitors for protein tyrosine phosphatases. These enzymes play an important role in controlling all intracellular signal transduction pathways, and inhibitors of phosphatases are useful for treating a variety of diseases including type II diabetes and infection by Yersinia pestis, the causative agent of bubonic plague. We have examined how the linker structure in a series of divalent inhibitors influences their potency, and discovered inhibitors with nanomolar activity against the Yersinia phosphatase. Three papers describe our continuing work to develop potent and selective inhibitors for a variety of proteases. Inhibitors of the serine protease plasmin have potential as cancer chemotherapeutic agents that are targeted toward the processes of metastasis and angiogenesis. We have also discovered that squaric/hydroxamic acid hybrids are a completely new motif for the design of matrix metalloprotease inhibitors. This study represents a new research direction for my group.
Our other three papers are in the general area of asymmetric catalysis. This is an area that is a major focus of current research in organic chemistry, and it is critical for the production of pharmaceutical agents and fine chemicals. Two of the manuscripts describe our discovery of modular amino acid-based catalysts for the enantioselective addition of vinylzinc reagents to aldehydes to yield chiral allylic alcohols. Using an iterative optimization strategy we have found catalysts for this reaction that give up to 95% enantiomeric excess and excellent yields. The final manuscript describes our use of an enzyme as high throughput tool to measure the enantiomeric excess of large numbers of samples. This work broadens our previously described EMDee procedure (enzymatic method to determine ee) by requiring the enzyme to simply bind to the analyte, rather than process it as a substrate. In this manuscript, we describe the application of this strategy to the analysis of chiral sulfoxides.
Awards
• Eli Lilly Predoctoral Fellow - Harvard University: 1991 - 1992
• United States Army Medical Research and Materiel Command: Breast Cancer Research Initiative - Career Development Award - Brown University: 1996 - 2000
• Salomon Faculty Research Award - Brown University: 1996 - 1998
• Award for Outstanding Academic Advising - Brown University: 2000
Affiliations
American Chemical Society
American Association for the Advancement of Science
Funded Research
National Institutes of Health - General Medicine: "A New Class of Serine and Cysteine Protease Inhibitors"; $850,931; 5/1/03 - 4/30/06
