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Researchers from UT Southwestern, the Czech
Republic and Germany studied the structure and inhibition properties
of the basic molecule as well as several variants with chains of other
atoms hanging off them. The researchers found that at very low
concentrations, the new molecules inhibit protease in infected
cultured human cells with no obvious toxicity toward the cells.
The 12-pointed, cagelike molecule of boron bound to
carbon, called carborane, has been known for more than 50 years but
just recently came to the attention of researchers in the Czech
Republic as a possible AIDS drug, Dr. Otwinowski said.
The Czech group bound the metallacarboranes they
were studying to the proteases, then brought the diffraction data to
UT Southwestern to have the structures interpreted. The structures
were determined by a process called X-ray crystallography, in which
the crystals are bombarded with X-rays, and then the patterns made
when the component atoms deflect the rays are deciphered.
The metallacarboranes appeared to occupy the
portion of the protease used to hold key proteins in place as part of
the infective cycle of HIV, preventing the proteases from working.
Other advantages are that the compounds are stable
and can be modified in many ways by attaching other strings of atoms
to them. Further research may reveal that one modified version may be
more stable or less toxic than another, for example. These compounds
were also found to bind to the protease in a different location than
the current class of protease inhibitors, so they may be effective
against HIV strains that have become resistant to that class.
Dr. Pavlina Rezacova, postdoctoral researcher in
biochemistry at UT Southwestern, also participated in the study, as
did researchers from the Academy of Sciences of the Czech Republic;
the Institute of Chemical Technology and Charles University in the
Czech Republic; the University of Heidelberg in Germany. |
