The interests of the Parquette group revolve
around the theme of synthetic macromolecular and
supramolecular organic chemistry. Particular emphasis is on
the design and synthesis of functional macromolecules
that fold into a well-defined chiral secondary
structure because these molecules have tremendous potential
to function as enantioselective catalysts, chemical
sensors and liquid crystals among many other applications
in materials science and molecular recognition.
The research goals can be broadly classified into
two categories: (a) developing molecules with
well-defined conformational properties and (b) utilizing
these materials in applications for which conformational
order is crucial for function. A major thrust is the
synthesis of intramolecularly hydrogen-bonded
dendrimers including those that adopt helical or propeller
conformations. The chiral conformational preferences of
these materials is also being exploited in
enantioselective catalysis. Other projects include the synthesis
of desymmetrized water-soluble amphiphilic
dendrimers and supramolecularly self-organizing dendrimers.
Also under investigation is the use of soluble
hyperbranched polymers as solid supports for oligosaccharide
synthesis and the development of low-viscosity,
high-strength dental restoratives from dendrimeric and hyperbranched materials.
The Lowary group uses synthetic chemistry to
assemble molecules for use in studies focused on understanding
the biological roles of carbohydrates. The major focus
is developing methodology for the syntheses of
oligosaccharides with furanose residues. The
first total synthesis of the terminal
hexasaccharide motif found in two mycobacterial
cell wall polysaccharides (Ara6) has been recently
completed. Current efforts include the synthesis of
inhibitors of the enzymes that assemble
furanose-containing oligosaccharides, which are expected to be
potential antibiotics active against tuberculosis and
other mycobacterial diseases. In collaboration with the
Hadad group, students in the Lowary group are studying
the conformation of these oligosaccharides. In addition
to the synthetic efforts mentioned above, these
studies include the chemical synthesis of isotopically
labeled carbohydrates, NMR studies, and
computational investigations. The utility of vibrational spectroscopy
on oxygen-18 labeled compounds as a method
for determining carbohydrate structure is being
investigated as well.
The Platz laboratory designs, synthesizes, and evaluates new light-activated sensitizers which bind viral nucleic acids. For example, flavins undergo light-induced electron-transfer reactions and cycloaddition reactions when bound to DNA and RNA of pathogens present in blood.
Students in the Hart group have interdisciplinary ties involving the synthesis of lipids for use as probes of membrane structure.
Bioorganic projects in the Coleman group include
the study of the DNA cross-linking of antitumor
agents, discussed above and the design of fluorescent
probes with which to study DNA bending. A coumarin
C-riboside has been synthesized using a
stereoselective palladium-catalyzed C-glycosidation reaction, and
this probe has been incorporated synthetically into DNA
oligonucleotides. Examination of this fluorescent base using the technique
of time-resolved Stokes shift spectros copy has allowed the picosecond
motions of DNA to be directly observed for the first time. This
coumarin system is also being incorporated into amino
acid probes with which to study the dynamic aspect
of protein folding.
Students in the Pei lab are currently studying several enzymes involved in protein posttranslational modifications: peptide deformylase, methionine aminopeptidase, and protein tyrosine phosphatases. Potent inhibitors and prodrugs are being developed against these enzymes using both rational design principles and combinatorial chemistry. The inhibitors against the deformylase have proven to be effective, broad-spectrum antibacterial agents, while inhibitors against the latter enzymes are expected to act as anticancer drugs.
