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Computational model of the rhodium catalyst developed by the UB
researchers.
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The chemical strategy Davies developed depends
on the use of proprietary catalysts his company manufactures.
Minute amounts of the rhodium-based catalyst can have a major impact,
he explained, with 1 gram capable of producing 10 kilograms of a
pharmaceutical product.
"So it's like a bit of 'golden dust' to get everything going," said
Davies, a researcher at UB's New York State Center of Excellence in
Bioinformatics and Life Sciences and president and chief executive
officer of Dirhodium Technologies.
"As rhodium metal costs 10 times the price of gold, the catalyst is a
high-value material," he said.
Available through chemical supply companies, the reagents are being
used by pharmaceutical scientists in both industry and academia.
Already, one major pharmaceutical company is using the reagents to
synthesize a compound now in clinical trials.
"Demand for our catalysts has gone from gram to kilogram quantities,
from fractions of an ounce to multiple pounds," said Davies.
So far, the new synthesis strategy has generated compounds that have
potential activity against a broad range of disease states, from
cancer to central nervous system disorders, such as depression, to
inflammatory and microbial diseases and medications for treating
cocaine addiction.
"This method is like an enabling technology, making available new
targets and materials that previously were out of range," said Davies.
Its ability to result in never-before-seen chemical structures is
making Davies' collaborations with scientists in partner institutions
on the Buffalo Niagara Medical Campus especially fruitful.
"We're using this as a platform for drug discovery, collaborating
through the Center of Excellence with biologists at UB, Roswell Park
and Hauptman Woodward Medical Research Institute," said Davies.
Davies' company is one of 10 life sciences spinoffs based in the
Center of Excellence, which has the dual mission of promoting life
sciences research while facilitating economic development in Upstate
New York.
In addition to helping drug companies design novel leads for new
products, the new chemistry also allows pharmaceutical companies to
synthesize efficiently and economically large quantities of novel
compounds.
Through catalysis, the chemical synthesis method the UB researchers
developed allows for highly unusual functionalizations of
carbon-hydrogen bonds, Davies explained.
"The method allows you to transform a molecule from a simple structure
to a much more elaborate, drug-like material," he said, "so it goes
from a cheap building block to a potential drug-like candidate.
Without a catalyst, it won't happen."
A major advantage of Davies' chemical strategy is that the resulting
compounds are produced selectively as single mirror images.
Pharmaceutical companies prefer to develop new chiral drugs (chiral
meaning "handed") as a single isomer because opposite mirror images
can have different biological effects and may be harmful.
"A small amount of our catalyst can be used to generate large amounts
of the active mirror image of the pharmaceutical ingredient," Davies
said.
The UB research has been funded by the National Institutes of Health
and the National Science Foundation, both of which were recently
renewed for a total of $1.6 million. The work also has been supported
by the UB Center for Advanced Biomedical and Bioengineering Technology
(UB CAT), located in the Center of Excellence.
The Nature paper was co-authored by James R. Manning, a graduate
student in the Department of Chemistry in the UB College of Arts and
Sciences.
The New York State Center of Excellence in Bioinformatics and Life
Sciences was created in Buffalo in 2002 as part of more than $200
million dollars in investment from state, federal, industrial and
philanthropic sources to create a hub of life sciences expertise and
innovation in Upstate New York. The COE brings a strong foundation in
life sciences research and discovery to its mission and collaborative
efforts with industry, government and researchers around the world to
improve the health and well-being of the population. The Center of
Excellence is a major UB research center; its research partners are
Roswell Park Cancer Institute and Hauptman-Woodward Medical Research
Institute.
The University at Buffalo is a premier research-intensive public
university, the largest and most comprehensive campus in the State
University of New York. UB's more than 28,000 students pursue their
academic interests through more than 300 undergraduate, graduate and
professional degree programs. Founded in 1846, the University at
Buffalo is a member of the Association of American Universities.
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