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Discodermia dissoluta
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| Treated cancer cells |
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The just announced 2010 Nobel Prize in Chemistry recognizes three international scientists who developed a technique called “palladium-catalyzed cross coupling" that has greatly enhanced the efficiency and precision of organic molecular synthesis in the laboratory. Among other things, the technique has enabled the synthesis of large, complex molecules that have potential as next-generation medicines in the fight against cancer, HIV, and other dread diseases.
The FAU Harbor Branch connection to the Nobel prizewinning research is a small Caribbean sponge known to marine taxonomists as Discodermia dissoluta. Specimens of this sponge collected in the Bahamas by Harbor Branch scientists Shirley Pomponi and John Reed almost a quarter-century ago were returned to the institute where natural products extracted from them could be evaluated for their pharmaceutical potential.
The research eventually resulted in the isolation and characterization of the compound discodermolide by Dr. Sarath Gunasekera (now at Smithsonian Marine Station in Fort Pierce, FL) and Dr. Ross Longley (now at Lake Erie College of Osteopathic Medicine in Bradenton, FL). Discodermolide has shown promise as an anticancer drug. The compound has a mode of action similar to the anticancer drug Taxol®, stabilizing the microtubule scaffolding of target cells, arresting them at a specific stage in the cell cycle and halting cell division. Discodermolide has shown efficacy against cancer cell that are resistant to Taxol and the two compounds utilized in tandem exhibit synergistic effects while reducing side effects.
The key impediment to early discodermolide research was a lack of readily available material. Continued harvest of a relatively a rare deepwater sponge that provides the target compound at very small yields would have been both economically and ecologically unsustainable.
The material supply issue was ultimately addressed via laboratory synthesis of discodermolide based on the palladium-catalyzed cross-coupling procedures devised by three recently announced Nobel laureate chemists, Richard F. Heck, Ei-ichi Negishi and Akira Suzuki.
Negishi’s variant of the cross-coupling reaction became a crucial step in discodermolide synthesis. Subsequently refinement of the synthetic process produced sufficient quantities of discodermolide to allow the initiation of human clinical trials in patients suffering from a variety of cancers.
Discodermolide is among the marine biomedical compounds currently available for licensing through the Florida Atlantic University Technology Transfer office.
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