Max
08-05-2001, 09:09 AM
Designer Chemical Offers Alzheimer's Hope
Library: MED
Keywords: ALZHEIMER'S BIOCHEMISTRY CHICAGO OKLAHOMA
Description: Researchers at University of Illinois at Chicago have designed
and synthesized highly potent inhibitor compounds that could lead to
effective Alzheimer's disease treatment. (Journal of Medicinal Chemistry)
August 2, 2001
Contact: Paul Francuch (312) 996-3457; francuch@uic.edu
DESIGNER CHEMICAL OFFERS ALZHEIMER'S HOPE
Researchers at the University of Illinois at Chicago have designed and
synthesized highly potent inhibitor compounds that could lead to an
effective treatment for Alzheimer's disease. The work was reported in the
American Chemical Society's Journal of Medicinal Chemistry.
Arun Ghosh, professor of chemistry, led the UIC research team in
collaboration with Jordan Tang, head of the Protein Studies department at
the Oklahoma Medical Research Foundation in Oklahoma City.
In earlier work, Ghosh and Tang designed an inhibitor that blocks the action
of one of two protein-cutting enzymes, called proteases, thought to be
responsible for Alzheimer's disease. This enzyme, called memapsin 2, severs
a longer protein in the brain called amyloid precursor protein, or APP, to
produce beta-amyloid, which accumulates in the brain and forms plaques that
lead to the development of Alzheimer's disease.
"This enzyme is probably the most exciting target for an Alzheimer's drug,"
said Ghosh.
Tang discovered the precise location where memapsin 2 cuts APP.
Subsequently, Tang and Ghosh demonstrated that a model inhibitor compound
attracts memapsin 2 and keeps it from cutting APP -- a promising way to halt
accumulation of beta-amyloid in the brain. That inhibitor was reported in
the Journal of the American Chemical Society last year and was shown to be
effective in test tube experiments.
The research team knew that while useful as a model, the inhibitor would not
be effective in drug therapy. "That was a preliminary inhibitor," said
Ghosh. "It's a big one, containing eight peptides -- a size that is
inconceivable to be a drug candidate."
Ghosh and his team set out to reduce the molecule's size in an effort to
increase its potential as a drug candidate.
"Peptide-like compounds never make useful drugs because they're
metabolically unstable, they're insoluble and, perhaps the biggest problem
in Alzheimer's patients, they're hard to deliver in the human brain," Ghosh
said. The molecule has to be small enough to cross what's called the
blood-brain barrier. "Peptide-like molecules are not very good at
penetrating this barrier. Our ultimate goal is to deliver a totally
non-peptide inhibitor," he said.
The current paper describes a new generation of inhibitors designed and
tested in the laboratory. These new inhibitors are still potent yet
substantially smaller, comparable in size to HIV protease inhibitor drugs
now being prescribed.
"Designing a smaller, more potent inhibitor is an important step in the
development of an effective treatment for Alzheimer's patients," said Tang.
The research is supported by grants from the National Institutes of Health.
The Alzheimer's Association reports about 4 million Americans now suffer
from the disease. It predicts that number will grow as the population ages,
unless a cure or prevention is found. Current treatments provide only
symptomatic relief.
-UIC-
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© 1995-2001 Newswis
__________________________________________________ __
Maksim (Max) Bily
mail to : imax@odyssee.net
----------------------------------------------------------------------------
---------------
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research info on Web
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Library: MED
Keywords: ALZHEIMER'S BIOCHEMISTRY CHICAGO OKLAHOMA
Description: Researchers at University of Illinois at Chicago have designed
and synthesized highly potent inhibitor compounds that could lead to
effective Alzheimer's disease treatment. (Journal of Medicinal Chemistry)
August 2, 2001
Contact: Paul Francuch (312) 996-3457; francuch@uic.edu
DESIGNER CHEMICAL OFFERS ALZHEIMER'S HOPE
Researchers at the University of Illinois at Chicago have designed and
synthesized highly potent inhibitor compounds that could lead to an
effective treatment for Alzheimer's disease. The work was reported in the
American Chemical Society's Journal of Medicinal Chemistry.
Arun Ghosh, professor of chemistry, led the UIC research team in
collaboration with Jordan Tang, head of the Protein Studies department at
the Oklahoma Medical Research Foundation in Oklahoma City.
In earlier work, Ghosh and Tang designed an inhibitor that blocks the action
of one of two protein-cutting enzymes, called proteases, thought to be
responsible for Alzheimer's disease. This enzyme, called memapsin 2, severs
a longer protein in the brain called amyloid precursor protein, or APP, to
produce beta-amyloid, which accumulates in the brain and forms plaques that
lead to the development of Alzheimer's disease.
"This enzyme is probably the most exciting target for an Alzheimer's drug,"
said Ghosh.
Tang discovered the precise location where memapsin 2 cuts APP.
Subsequently, Tang and Ghosh demonstrated that a model inhibitor compound
attracts memapsin 2 and keeps it from cutting APP -- a promising way to halt
accumulation of beta-amyloid in the brain. That inhibitor was reported in
the Journal of the American Chemical Society last year and was shown to be
effective in test tube experiments.
The research team knew that while useful as a model, the inhibitor would not
be effective in drug therapy. "That was a preliminary inhibitor," said
Ghosh. "It's a big one, containing eight peptides -- a size that is
inconceivable to be a drug candidate."
Ghosh and his team set out to reduce the molecule's size in an effort to
increase its potential as a drug candidate.
"Peptide-like compounds never make useful drugs because they're
metabolically unstable, they're insoluble and, perhaps the biggest problem
in Alzheimer's patients, they're hard to deliver in the human brain," Ghosh
said. The molecule has to be small enough to cross what's called the
blood-brain barrier. "Peptide-like molecules are not very good at
penetrating this barrier. Our ultimate goal is to deliver a totally
non-peptide inhibitor," he said.
The current paper describes a new generation of inhibitors designed and
tested in the laboratory. These new inhibitors are still potent yet
substantially smaller, comparable in size to HIV protease inhibitor drugs
now being prescribed.
"Designing a smaller, more potent inhibitor is an important step in the
development of an effective treatment for Alzheimer's patients," said Tang.
The research is supported by grants from the National Institutes of Health.
The Alzheimer's Association reports about 4 million Americans now suffer
from the disease. It predicts that number will grow as the population ages,
unless a cure or prevention is found. Current treatments provide only
symptomatic relief.
-UIC-
home · scinews · mednews · biznews · lifenews · search · contact
© 1995-2001 Newswis
__________________________________________________ __
Maksim (Max) Bily
mail to : imax@odyssee.net
----------------------------------------------------------------------------
---------------
Visit http://carecure.rutgers.edu/spinewire/index.html for best sci
research info on Web
www.thinkwave.com (http://www.thinkwave.com) -Where Teachers, Students and Parents Communicate
Play International Red Cross Lottery online
for weekly jackpot of 20.000.000 Swiss Franks tax free...
http://www.pluslotto.com/default.asp?urlref=3300003298889