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Researchers at University of the Pacific have designed a model for an anti-cancer drug that could lead to safer, more effective cancer treatment and drug development. The proposed drug is derived from enediynes - natural substances produced by microorganisms found in soils in Texas and Argentina during the 80's. With slight but crucial modifications, the enediynes can be "trained" to attack only cancerous tumors, leaving the surrounding healthy tissue alone and greatly increasing the survival rate of cancer treatment.
Enediynes are masterpieces of natural ingenuity and share a common mechanism, namely to cut like scissors through the DNA of a cell, said Professor Elfi Kraka, former chair of Pacific's Chemistry Department.
"Microorganisms have had two billion years more experience than humans have in figuring out how to fight toxic bacteria and viruses," Kraka said. "In this time, they have developed compounds such as enediynes. Now we have to learn how to adjust nature's design to our needs."
Kraka and Professor Dieter Cremer, director of nanotechnology at Pacific, conducted the research with the assistance of a team of graduate students from all over the world.
Their research was published on March 6 in the American Chemical Society's The Journal of Physical Chemistry B and is recognized by the organization as a potentially major breakthrough in cancer research. The article, "Design of a New Warhead for the Natural Enediyne Dynemicin A.: An Increase of Biological Activity," may be found on the Web at dx.doi.org/10.1021/jp0773536.
In their report, the researchers describe using enediynes to develop an anti-cancer "warhead" that targets the acidic signature of tumor cells. Unfortunately, naturally occurring enediynes that are currently used in cancer treatment are as destructive to healthy tissues as tumor cells and therefore lead to undesirable side effects.
The Pacific researchers learned through computer-assisted drug design that by combining enediynes with amidines, compounds also found in nature, they can create a warhead that only is activated in acidic environments. Contrary to healthy cells, cancer cells generate an acidic environment. Therefore the warheads will only attack the DNA strands of the cancer cells, thus destroying them.
"Often cancer patients suffer severely from cancer treatments based on chemotherapy," Kraka said. "This new drug model has a lot of potential and could lead to a new efficient anti-cancer drug with highly reduced side effects."
Kraka and Cremer conducted the essential steps of their research after joining Pacific. Their research interests include theoretical and computational chemistry, nanotechnology, and computer assisted drug design. They are currently looking for a pharmaceutical company that would be interested in trying to develop their new drug model and help them test it.
"The breakthrough that Professor Kraka and her team have made could have a tremendous impact on the treatment of one of the most significant diseases of our times," Provost Phil Gilbertson said. "There are very few homes that would not be affected by this potentially groundbreaking drug model as families across the country and throughout the world can claim a relative who has suffered from this terrible disease."
About University of the Pacific
Pacific is a one of west's most distinctive, student-centered national universities. We are a private university with about 6,700 students on three campuses in Northern California. We offer undergraduate, graduate, and professional degree programs in nine colleges. Compared to most schools our size, we offer a broader array of courses. We are one of a few smaller schools ranked highly as a "best value" by U.S. News and World Report.
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