Molecules With Potential To Treat Breast Cancer Discovered
- Date:
- May 4, 2007
- Source:
- Hamilton College
- Summary:
- Hamilton College researchers have identified molecules that have been shown to be effective in the fight against breast cancer. The Hamilton researchers used state-of-the-art computational techniques in a novel way to design molecules that they predicted would be effective lead compounds for breast cancer research.
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Hamilton College researchers have identified molecules that have been shown to be effective in the fight against breast cancer. The Hamilton researchers used state-of-the-art computational techniques in a novel way to design molecules that they predicted would be effective lead compounds for breast cancer research. Scientists from the Albany Medical College subsequently synthesized the predicted molecules and showed that they were indeed potential anti-breast cancer compounds in animal systems.
Breast cancer is the most common cancer among women and tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment. Many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Consequently, there is an ongoing need for breast cancer drugs that have different molecular targets.
Previous work by the Albany Medical College researchers had shown that 8-mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat models, interacting with an unsolved receptor, while peptides smaller than eight amino acids did not.
The Hamilton researchers used advanced computational methods to predict the structure and dynamics of active peptides, leading to discovery of smaller peptides with full biological activity. The results were used to identify smaller peptides with the three dimensional structure of the larger peptides. These peptides were synthesized and shown to inhibit estrogen-dependent cell growth in a mouse uterine growth assay, a test showing reliable correlation with human breast cancer inhibition.
Winslow Professor of Chemistry George Shields and co-director of the Center for Molecular Design Karl Kirschner led the Hamilton research team with undergraduate students Katrina Lexa ‘05, Amanda Salisburg ‘08, Katherine Alser ‘09. The Albany team consisted of Leroy Joseph, Thomas Andersen, James Bennett, and Herbert Jacobsen of Albany Medical College.
The results reported in the published article were first presented by Professor Shields at the 2006 International Symposium on Theory and Computations in Molecular and Materials Sciences, Biology and Pharmacology, on February 26, 2006, St. Simon’s Island, Ga.
A paper detailing the research, “Computational Design and Experimental Discovery of an Anti-estrogenic Peptide Derived from Alpha-Fetoprotein,” will be published in the May 16 issue of the Journal of American Chemical Society.
This work was funded by the National Institutes of Health, the New York State Breast Cancer Research and Education fund, the Department of Defense's Breast Cancer program, and the National Science Foundation.
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