Contact: Gary Shultz (214) 768-7650, [email protected]
Oct. 26, 1998
SMU CHEMISTRY PROFESSOR DEVELOPS STRONGER COMPOUNDS IN FIGHT AGAINST INFECTIONS
DALLAS (SMU) ó New, highly potent compounds that effectively treat penicillin-resistant infections have been developed by a research chemist in Southern Methodist University's Dedman College.
"Bacteria have developed a resistance enzyme that destroys penicillin, and the problem is worsening as the bacteria exchange and spread genetic information coding for this resistance," said Buynak, whose research has been supported by the National Institutes of Health, Lederlee Laboratories, Petroleum Research Fund and Robert A. Welch Foundation.
Penicillin, developed into a therapeutic drug in 1940, is one of the most widely used antibiotic agents in the world because it kills many of the common bacteria that infect humans. In recent years, however, penicillin-resistant bacteria have begun to evolve, making it more difficult to treat many illnesses, including streptococcal infections, syphilis, diphtheria and anthrax.
Buynak has developed four new classes of compounds, called beta-lactamase inhibitors, which can defeat resistant bacteria's protective defenses without harmful side effects to humans. These compounds are then co-administered, together with an antibiotic, to kill the resistant strains. Three of the new classes of compounds have already been patented and the fourth is pending. These inhibitors deactivate the bacterial enzyme beta-lactamase, which destroys penicillins and cephalosporins.
Each of the new classes contains several, highly biologically potent individual compounds. Finding the best drug candidate in each class of these new molecules is the topic of research underway in Dr. Buynak's lab.
"We have more than a dozen compounds which are much better than anything on the market in terms of their ability to inhibit the isolated (beta-lactamase) enzymes. It's now a matter of finding the compound which is best at penetrating the bacterial cell wall and which is most easily tolerated by the patient." says Buynak.
"Our goal has been to develop a molecule that can be used against as many different types of bacteria as possible so that physicians can easily treat an infection without the need to identify the specific organism involved," said Buynak. "We are trying to stay one step ahead of the bacteria as they develop defense systems to protect themselves."
Bacteria become resistant to antibiotics by mutation or by acquiring a plasmid, which is an extra piece of DNA in addition to the cell's chromosome. Those who track the evolution of the resistant strains of bacteria say that factors contributing to the development and evolution of such bacteria include physicians' willingness to prescribe antibiotics for even mild cases of infection, patients who do not take their full prescriptions and hospitals that use antibiotics as a preventative measure before surgery and other medical procedures.
Buynak, although trained as a synthetic chemist, uses modern technology in his research.
"In addition to actually mixing the chemicals and making the molecules, we also use sophisticated software on SGI computers to three-dimensionally model the large biological targets and to predict which new small molecules will be the best inhibitors. We also do our own preliminary biological evaluations against isolated enzymes," Buynak said.
The chemistry professor is closely allied with the pharmaceutical industry which verifies his results. The patents have been filed with the help of Research Corporation Technologies, a technology transfer company which has taken an interest in his research.
"SMU and Dedman College have been instrumental in helping to provide the hardware and software to get me started with the molecular modeling. I have also been assisted by Dr. George Ford (of SMU's Chemistry Department), who is our resident computational expert," he said.
Born in Ohio, Buynak received his Bachelor of Science degree from Case Western Reserve University in 1975 and his Ph.D. from Rice University in 1980. He was a postdoctoral fellow at Yale University before joining SMU's Department of Chemistry in 1981. His research focuses on the design of enzyme inhibitors, the synthesis of beta- lactamase antibiotics and the synthesis of strained molecules. He has written numerous articles for professional journals, made presentations at professional conferences and is a popular lecturer. He is a referee or reviewer for the National Institutes of Health, National Science Foundation, Petroleum Research Fund, Journal of Organic Chemistry and Journal of the American Chemical Society. He serves on SMU's Health Professions Recommendation Committee.
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