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Natural Product Libraries
Roecker has also participated in several combinatorial chemistry
projects, developing solid phase chemistry and producing natural
product libraries for biological screening purposes.
"This is the kind of science that serves as the foundation
to the drug discovery process," says Nicolaou.
The advantage of using libraries of natural products to
screen for drug candidates is that these natural products
inhabit that part of the chemical universe that may be the
most practical place to look for drugs. Nature has designed
these chemicals with many of the correct properties already—they
are generally small, soluble, and have already been designed
by nature to do certain things, like stop bacteria from growing.
Roecker worked on a natural product-like library using a
motif common in a lot of drugs called a 2,2-dimethylbenzopyran.
His work included designing chemistry to put the benzylpyran
onto a solid phase in order to make a library of the 10,000
compounds. And recently, he has been looking for biological
applications for the library.
"He and his teammates invented numerous enabling technologies
for combinatorial chemistry," says Nicolaou. "Screening of
the libraries led to the discovery of a number of antibacterial
agents, enzyme inhibitors, and receptor agonists and antagonists."
"It's fun to work with a lot of good chemists," says Roecker.
"My peers, the other graduate students and postdocs in the
laboratory, have a lot of different experiences. I try to
keep my eyes and my ears open and gain as much knowledge as
I can from reading the literature and listening to other people."
Combinatorial Chemistry for the Masses
Wolkenberg has some experience with combinatorial chemistry
of a different sort.
With Andrew Su, another student in the chemistry program,
Wolkenberg became involved in the summer outreach program
at TSRI, which brings local high school science teachers,
mainly of biology, to TSRI where they get hands-on laboratory
experience.
"We were thinking, 'what could we possibly bring that is
going to be useful for them?'" says Wolkenberg, who taught
these teachers for the past two years. "We ended up thinking
about drug discovery."
Wolkenberg and Su came up with an exercise for high school
classrooms that involves discovering a drug using the techniques
of combinatorial chemistry. The students make a mixture of
compounds and then screen for biological activity against
bacteria. Then, from those that work, the students deconvolute
the mixtures to determine which compound has the active ingredient.
And thus students discover a drug; simple, fun, and brilliant.
"It ended up being a huge success," says Wolkenberg, who
published, with Su, an article on the laboratory and the experience
in the Journal of Chemical Education. "It was a great
experience."
One Award to Rule Them All...
The fellowships offer one year of support plus money for
expenses, including a trip to next year's National Organic
Symposium (sponsored by the ACS Division of Organic Chemistry),
at which the fellows will present a poster on their work.
"It's a great fellowship program," says Boger. "One that,
through the years, quite a few people at Scripps have been
successful at competing for."
For their applications, both fellows had to write a mini-review
of a subject not necessarily related to their own research.
Roecker chose to write about organic catalysis, following
this field from its roots in the laboratories of the 1970s
to its practice in the labs of today—including several
in his department in rooms right down the hall. "It's very
interesting to use chiral organic molecules to induce selectivity
in reactions," he says.
Wolkenberg wrote about the in situ activation of anti-cancer
alkylating agents. This involves compounds that are inert
but are modified into some active form, becoming reactive,
when they reach their target.
After Wolkenberg was done with the mini-review, he kept
going, turning it into a full-fledged review he submitted
with Boger to Chemical Reviews last month.
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