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Now, a University at Buffalo medicinal chemist is
hoping to change that.
Matthew D. Disney, Ph.D., assistant professor in
the Department of Chemistry in UB's College of Arts and Sciences, is
working to develop rules for targeting RNA. These rules could be used
in the rational design of compounds to inhibit a specific RNA sequence.
Disney's goal, with the help of a five-year,
$50,000 new faculty award from the Camille & Henry Dreyfus Foundation,
is to develop a chemical code to enable rational design of binders to
any RNA structure. His work also is funded by the New York State
Center of Excellence in Bioinformatics and Life Sciences.
"What we would like to do is develop a general set
of tools that can take an RNA sequence and design efficiently a
compound that can turn its activity off," explained Disney.
The human genome and other sequencing efforts have
uncovered a lot of sequence information, he continued, but the
question, he asks, is, "How can that information be best exploited?"
"One answer may be to take RNA sequence information
and design drugs that target that sequence," said Disney. "If that can
be done, then a lot of the expense in designing new drugs goes out the
window."
Potentially, that could facilitate the development
of compounds to treat diseases ranging from antibiotic-resistant
bacterial infections to cancer and genetic diseases, such as sickle
cell anemia and cystic fibrosis, Disney said. Rationally designed RNA
inhibitors could, he explained, prove more valuable than molecules
that inhibit DNA. One reason is that while DNA bases or nucleotides
are always paired according to the same formula, RNA bases have more
diverse pairings, which makes targeting RNA more challenging, but also
potentially more valuable.
"The ability to form different pairings allows RNA
to have a much larger structural repertoire than DNA and that gives
RNA the ability to have such diverse cellular functions," said Disney.
In addition, he said, because DNA is present only
in the nucleus, pharmaceutical compounds that target it must be able
to penetrate the nucleus.
"Since RNA is present both in the cell's nucleus
and cytoplasm, you do not need to get a compound into the nucleus to
target it," he said.
Because RNA folds more like a protein than DNA does,
it also may be easier to design compounds that selectively target
specific structures, he added. Disney lives in Williamsville. |
