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- B.Ch.E., Cornell University, 1966
- M.S., Ch.E., Cornell University, 1966
- Ph.D., Polytechnic University, 1971
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Research Interests |
Research: Peptide, Biopolymer and Biochemistry
My
research interests involve the synthesis, conformational activity and
biological relevance of peptides and studies on pepetide receptor
interactions.
1)
We synthesize peptides and prenylated peptides using a combination of
solution phase and solid phase procedures. Presently, we are interested
in two mating pheromones from Saccharomyces cerevisiae, a-factor and
a-factor. The former is a linear tridecapeptide whereas the latter is a
farnesylated peptide, and is representative of a new class of molecules
containing this novel post-translational modification. Our group has
been active in developing techniques for the efficient synthesis of
farnesylated peptides which are then subjected to biophysical and
biochemical investigation.
2)
The biological activity of peptide hormones implies that these
molecules assume a specific conformation when they bind to their target
receptor. We have actively pursued the biologically active conformation
of the a-factor using circular dichroism, nuclear magnetic resonance
and vibrational circular dichroism studies. Both linear analogs of the
pheromone and analogs with covalent constraints have been prepared and
studied. Based on these results we have hypothesized an "active
conformation and are trying to apply techniques such as rotational-echo
double-resonance spectroscopy (REDOR) to study the pheromone bound to
its receptor.
3)
An important goal of our studies is understanding the structure of the
a -factor receptor which is a G protein-coupled receptor. Toward this
end we have participated in purifying this receptor to homogeneity and
have been synthesizing fragments of the receptor for biophysical
analysis using circular dichroism and nuclear magnetic resonance
spectroscopy in solution and the solid state.
4)
Peptides are sources of amino acids and nitrogen for cells. We are
studying the uptake of peptide by single cell eukaryotes such as the
yeast Saccharomyces cerevisiae and the pathogenic fungus Candida
albicans. These studies resulted in the discovery of the PTR family of
peptide transporters which are now known to exist in human intestine
and human kidney. Recently, we discovered another family of
oligopeptide transporters (OPT) which exist in certain fungi. These
studies provide fundamental information on molecular transport
phenomena and may be useful in the design of antifungal drugs. |
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