Cottrell Scholar Awards - 2016
Fluorinated Peptides and Proteins for 19F MRI and Integrated Research Experiences in an Organic Chemistry Lab Course
Magnetic Resonance Imaging is used by physicians to examine tissues inside living bodies, but scientists also use it to study molecular interactions in a test tube
William Pomerantz, assistant professor of chemistry, University of Minnesota, is working to improve on MRI techniques using the element fluorine due to its unique properties.
Observing the interactions between two proteins is a challenging task in the complex environment of a living cell. To do so, researchers “tag” a protein so that it is visible amidst many other biological background signals in a way that does not perturb the natural function of the protein. Fluorine offers special promise for this visualization. The fluorine atom is absent from the biological recipes for making all three essential biomolecules (proteins, sugars and nucleic acids) but is similar in size to the hydrogen atom. By tagging proteins with a variety of fluorine atoms replacing hydrogen, this gives researchers a specific probe to study proteins without background noise.
In addition to imaging a particular molecule involved in disease, understanding how molecules interact or bind with proteins is essential to developing new drugs. Pomerantz and his research associates hope to improve what is called fluorine-19 NMR spectroscopy to better understand the binding process.
(The initials NMR and MRI refer to the same process, nuclear magnetic resonance imaging. The medical community usually refers to it as MRI, while scientists prefer NMR. Fluorine-19 is an isotope of the element fluorine. Isotopes are atoms of an element with different numbers of neutrons in their centers (nuclei). Spectroscopy is the study of the interaction between matter and electromagnetic radiation.)
Specifically, Pomerantz seeks to develop design rules for using fluorine-19 tagged peptides (smaller parts of proteins) for imaging diseased tissue and tracking the peptides’ distinctive MRI signals as they attach to larger molecules. Current fluorine markers suffer from stability problems, poor physicochemical properties, and long retention times in the body. Through synthesizing peptides, Pomerantz predicts he and his colleagues will be able to both fine-tune how the peptides are broken down in the body, as well as provide well-behaved and highly sensitive signaling for imaging.
For the education component of the Cottrell Scholar Award, Pomerantz will make curricular changes for the first- and second-year undergraduate organic chemistry laboratory experience in collaboration with Gustavus Adolphus College. The changes will be aimed at retaining students in science and technology fields by providing early research experiences to undergraduates within their major fields of study. The course design integrates the drug discovery research program in the Pomerantz lab using fluorinated proteins with molecular design and synthesis of new organic molecules for binding to the proteins. These experiments will provide students with first-hand experience of the how molecules interact with proteins.