While some people joke that they will save the world or find the cure for cancer over summer vacation, Kathleen Naughton '08 (Cromwell, Conn.) comes closer to the truth of that joke than many. This summer she has an Emerson grant to do research on a project titled, "Experimental Investigation of the Solution Structures for Bioactive Peptides Derived from Alpha-Fetoprotein." Previous research suggests that these protein peptides have potential to inhibit and even treat cancers linked to estrogen. She will be advised by Robin Kinnel, the Silas D. Childs Professor of Chemistry.
Alpha-fetoprotein, or AFP, is produced by the fetus during pregnancy and released into the mother's bloodstream. Studies show that women who have been exposed to AFP are less likely to develop breast cancer or other estrogen-driven cancers.
Researchers have used molecular modeling programs to examine the activity of smaller peptide chains and sequences of as few as 8 amino acids out of the hundreds in the protein have retained their activity. Last summer, the Winslow Professor of Chemistry George Shields found that a chain of only four amino acids, the 4-mer TPVN, also remained effective. In other words, TPVN behaves much like the whole protein, especially in its cancer-inhibiting properties. As Naughton explains, "these four amino acids are the important part of the protein's anti-cancer function."
Shields' results, following the tenet of biology that "form follows function," suggest that the anti-cancer capabilities of the protein and its derivative peptide are dependant on the molecule's conformation, its arrangement in space.
In order to know how the molecule will behave in the real world, it is essential to study the real molecule. Naughton will study the solution structure of TPVN using the department's new NMR (nuclear magnetic resonance) machine, which she says is "probably the most powerful tool modern chemists have [and] the key of the project." NMR is related to MRI, and allows the chemist to determine the connectivity of atoms in a molecule based on their response to a strong magnetic field and a broadband radiofrequency pulse.
Naughton spent the first part of the summer working with the NMR, learning how to run the more advanced two-dimensional experiments essential to evaluating large and complicated molecules. She is now moving into the experimental part of her work, where she will run the peptide on the NMR. Now that she has acquired and purified the TPVN, she and Professor Kinnel are starting their experimentation.
Especially important is the NOESY experiment, which shows interactions between molecules close to each other in space. They expect that this experiment should show turns in the peptide, structural features essential to its physical properties.
TPVN, as mentioned above, has potential to be an anti-cancer drug. Proteins are large, and cannot be administered as drugs, but a chain of four amino acids is far more promising as a pharmaceutical. The challenge is in keeping the TPVN from simply being digested, but this is a problem which is easily solved by protecting groups.
Naughton, a chemistry and creative writing major, came to research because "I wanted to try it" and in hopes of gaining more laboratory experience. Her work this summer is funded by the Emerson Foundation Grant Program, which allows students significant opportunities to work collaboratively with faculty members, researching an area of interest.
-Lisbeth Redfield
