"This molecule has all the characteristics of a good starting point for a new class of compounds," said Dr. Zbyszek Otwinowski, associate professor of biochemistry at UT Southwestern and an author on the study, which appears in the Proceedings of the National Academy of Sciences and is currently available online.
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 cycl
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
31-Oct-2005