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By Tim Stoddard
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John Porco (from left), Scott Schaus, and John Snyder are developing a new kind of chemical library at the CAS Center for Chemical Methodology and Library Development. James Panek is not pictured. Photo by Fred Sway |
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In the race to churn out new blockbuster drugs, pharmaceutical companies
are hitting a wall in the development process. The chemical libraries
they use to synthesize complex drugs are fundamentally limited, says
John Porco, a CAS assistant professor of chemistry and a MED assistant
professor of pharmacology, and the poor selection is stifling innovation.
For Porco and other organic chemists outside of industry, there’s
an additional concern: the comprehensive libraries held by big pharmaceutical
companies are the best collections out there, and they’re not freely
accessible to academia.
In an effort to revitalize chemical libraries
in the public domain, the National Institute of General Medical Science
(NIGMS) of the National
Institutes of Health last year awarded a $10.6 million grant to a team
of Boston University chemists to create the Center for Chemical Methodology
and Library Development (CMLD). It is the largest grant ever received
by the chemistry department and “puts Boston University at the
forefront of one of the most exciting frontiers of synthetic organic
chemistry,” says Thomas Tullius, a CAS chemistry professor and
department chairman. Directed by Porco, the center is pioneering new
methods for synthesizing and purifying a more diverse library of molecules.
A
chemical library doesn’t look very much like Mugar or other paper-based
repositories of literature. It consists of thousands of small liquid
samples of molecules contained in compact square containers. At CMLD,
researchers are using new techniques to synthesize molecules that are
not available in existing libraries. Like a jukebox selecting a song,
a robot can retrieve a desired molecule from the library and provide
information on its structure and on how it was prepared. In addition,
researchers eventually will be able to borrow samples from the library
and use them in their own laboratories.
Over the next two years, CMLD
will replace the chemistry department’s
existing fourth floor laboratories at 590 Commonwealth Ave., but when
the new Life Science and Engineering Building is completed, the center
will relocate to those facilities.
Along with Porco, CMLD’s principal
investigators are James Panek and John Snyder, both CAS professors of
chemistry, and Scott Schaus,
a CAS assistant professor of chemistry. All four have trained in organic
chemical synthesis, but each brings a different subspecialty to CMLD. “We
approach problems from different directions,” says Schaus, “and
only by taking advantage of that were we able to assemble a cohesive
grant proposal.”
That diversity of expertise was one of the factors
that impressed NIGMS. “We
are very excited by the obvious synergy among the investigators as well
as the very thoughtful and complete plans that they presented for their
core facility and for outreach to the research communities,” says
John Schwaub, the NIGMS chemist who spearheaded the CMLD initiative.
The problem with existing chemical libraries, says Porco, is that they
all come from the same stock of basic chemicals. Larger manufacturers
such as Pfizer and Glaxo-Smithkline, as well as academic institutions
such as Boston University, all buy their simple stock chemicals, the
building blocks for bigger molecules, from the same suppliers. That lack
of diversity in building materials is already limiting the range of products
that chemists can ultimately build, Snyder says. “There’s
a need to make new kinds of building blocks for this library,” adds
Porco.
The primary goal of CMLD is to build a better library, but ultimately
the molecules housed there will be useful in medicine and in answering
basic questions in biology. “We’re not trying to set up a
small pharmaceutical company here at BU,” says Schaus. “We’re
actually interested in making compounds that you can use to study biological
functions.”
Researchers from Harvard Medical School, Yale, and BU’s
biology department are already clamoring to access the center’s
library, says Thomas Gilmore, a CAS biology professor. Gilmore is the
director
of CMLD’s Chemical Library Consortium, an affiliation of chemists
and biologists in the Boston area who collaborate on research projects
tied to the new library. “The consortium was organized at the NIH’s
request for CMLD to have a component of outreach for the biological community,” Porco
says. In addition, the library’s collection will eventually be
freely accessible on the Web (www.bu.edu/cmld).
New molecules designed
at CMLD could have potential pharmaceutical applications, says Gilmore.
Diseases arise when proteins misbehave, but molecules made
in the lab can stick to wayward proteins and enhance their function or
disable them entirely. For Gilmore, who studies a faulty protein involved
in various leukemias, the center could yield a useful compound for treating
cancer.
“
The applications aren’t limited to obvious medical purposes, like
refining a drug,” he adds. “The library can help a lot of
people who are doing basic research in biology.” For researchers
studying biological processes — the unfurling of a leaf, say, or
the regenerating limb of a salamander — the library could provide
new tools for understanding the nature and function of proteins that
are key to
these processes.
CMLD incorporates teaching into its research agenda.
There are numerous opportunities for undergraduate and graduate students
to work with faculty
in developing and applying the chemicals in the library. “The chemistry
department already has a very vigorous undergraduate research component,” Panek
says, “and we are emulating that with the new center.” For
more information about CMLD, see www.bu.edu/cmld.
14
November 2003
Boston University
Office of University Relations