Molecules With Potential To Treat Breast Cancer Found

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


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.



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.



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.



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.



Founded in 1879, the Journal of the American Chemical Society is the
flagship journal of the American Chemical Society and the premier medium
for the worldwide publication of fundamental research in all areas of the
chemical sciences. It is the most highly cited chemistry journal.



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.



The project was sponsored in part by the Department of the Army under
contract # W81XWH-05-1-0441. The U.S. Army Medical Research Acquisition
Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding
and administering acquisition office. The content of the information does
not necessarily reflect the position or the policy of the Government, and
no official endorsement should be inferred.



It was supported by the New York State Breast Cancer Research and
Education Fund through Department of Health Contract # C017922. Opinions
expressed are solely those of the author and do not necessarily reflect
those of the Health Research Science Board, the New York Department of
Health, of the State of New York.



This material is based upon work supported by the National Science
Foundation under Grant No. (CHE-0457275). Any opinions, findings, and
conclusions or recommendations expressed in this material are those of the
author(s) and do not necessarily reflect the views of the National Science
Foundation.



Part of the Federal support came from the National Institutes of
Health/National Cancer Institute. Federal money represents $475,870 or 82%
of total project costs; non-federal funds equal $100,000 or 18% of total
project costs.


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