Designing drugs and knowing exactly how they work may have just gotten easier, thanks to researchers at Georgia Institute of Technology.

Using a scanning force microscope, two chemistry graduate students and their research advisors have developed a new way to examine and quickly map how nucleic acid ligands, in some cases anti-cancer drugs, bind to and alter DNA at the molecular level.

This new method works by imaging individual DNA molecules. It's faster than traditional methods, and the results are direct and relatively simple to interpret.

"Our technique directly visualizes individual DNA molecules, while traditional techniques are indirect and inferential, sometimes giving inexplicable results," said Dr. Loren Williams, an associate professor in Georgia Tech's School of Chemistry and Biochemistry who serves as co-advisor to the project.

"Now when a medicinal chemist synthesizes a potential drug, we can very quickly tell them if it binds to DNA, how tightly it binds, and the mode by which it binds," he added.

One of the major advantages of the new assay is it shows researchers how drugs affect single DNA molecules, said Dr. Lawrence Bottomley, a Georgia Tech chemistry professor who specializes in scanning force microscopy.

"Other techniques require us to examine several billion molecules at a time and then make inferences about the behavior of individual molecules," he said.

Fourth-year graduate student Joseph E. Coury, working under Bottomley's direction, is responsible for much of the development of the new assay. Third-year graduate student Lori McFail-Isom, a student of Williams', prepared highly purified drug-DNA samples for the project and currently is obtaining images of new DNA complexes.

Williams and Bottomley presented this work during the 211th American Chemical Society national meeting in New Orleans in late March, and have submitted it
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Contact: Amanda Crowell
amanda.crowell@gtri.gatech.edu
404-894-6980
Georgia Institute of Technology Research News
23-May-1996