Our work currently relates to three areas: i) juvenile hormone
(JH) metabolism; ii) biomimetic polyene cyclizations; and iii) the
development of new enzyme mimics. While the specific goals for each
project varies, they all ultimately relate to better understanding
how enzymes catalyze chemical transformations. To do so, we utilize
a combination of organic, biochemical, and computational methods.
Development of Insect Juvenile Hormone Inhibitors
Insects control their growth, morphology, behavior, and sexuality
with a complicated array of hormones. We are interested in understanding,
at the molecular level, how the insect hormone, JH, is made and
then use this information, construct compounds that will selectively
inhibit its formation. Three specific enzymes related to JH production
are currently under investigation, including prenyltransferase,
farnesol dehydrogenase, and isopentenyl diphosphate isomerase. The
long range goals of this project is to provide new targets for insecticide
development.
Biomimetic Polyene Cyclizations
Bimimicry is the process whereby natural processes are duplicated
under artificial conditions. In this regard, we are actively pursuing
the development of new methods for steroid and related polycycle
production, that mimic naturally-occurring enzymes. Zeolites, or
molecular sieves, are both porous and acidic inorganic materials,
which we believe can function as surrogates of polyene cyclization
enzymes, such as oxidosqualene cyclase. Development of this type
of cyclization methodology could greatly expand the chemistÕs
synthetic repertoire by allowing the preparation of both naturally
occurring and unnatural compounds.
Antibody-Assisted Chemical Transformations
Antibodies, prepared from the immune systems of higher organisms,
are highly efficient receptors. While their overall structures are
quite similar, antibodies contain a binding region which has been
fine tuned for a specific antigen. This characteristic can be used
to prepare proteins that serve as either chiral templates for regio-
and/or enantioselective chemical reactions or as catalysts. The
latter "abzymes" have the potential of performing transformations,
which are thus far inaccessible using chemical or enzymatic methods.
We are currently utilizing antibody technology to develop novel
detoxifying agents.