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Journal of Undergraduate Research

Keywords

cancer, chemotherapy, anti-tumor, Geldanamycin, GA

College

Physical and Mathematical Sciences

Department

Chemistry and Biochemistry

Abstract

Cancer is a condition unlike any other known to man. It is one of the leading causes of death in the United States. In 2000, over 500,000 deaths resulted from various cancers.1 This has led to an extensive search for improved ways to treat cancer, and has left a daunting challenge to develop new ways to treat this condition. The natural product Geldanamycin (GA), the most potent of the benzoquinone absamycin antibiotics, has shown to have great promise as an anti-tumor agent. The analog of Geldanamycin, 17-Allylanino-GA, is currently in clinical trials2, and the first total synthesis of GA was recently completed in the Andrus Labratories.3 GA binds heat shock protein 90 (Hsp90), a 90 kDA protein essential for the development of new proteins in developing cells, whereas mature cells remain unaffected. A recent publication in Nature4 describes bioassays performed using 17-Allylamino-GA, wherein the drug has been shown to bind Hsp90 up to 100 times more tightly in cancer cell lines than in normal cell in vivo. A new analog is currently under development in the Andrus Laboratories, which could potentially increase the binding to Hsp90 with even greater affinity than ever, and decrease the toxicity of Geldanamycin to human biological systems.

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