- Chemical Biology: peptidomimetics
- Organic Chemistry: organic synthesis
- Analytical & Bioanalytical Chemistry
Research Summary
My lab seeks to develop new chemical probe molecules for protein-protein interactions (PPIs) by developing new chemistry and structural biology approaches. Broadly speaking, our research seeks to understand the molecular level details of PPIs. At the same time we use chemistry to design synthetic molecules that disrupt the dysregulated forms of PPI communication to further understand the underlying biology. We apply NMR, and in future experiments MRI, to visualize biomolecular interactions, and use small molecules that we synthesize in the laboratory to perturb the protein function. We use the element fluorine to facilitate our research goals 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, we “tag” a protein so that it is visible amidst many other biomolecular background signals in a way that does not perturb the natural function of the protein. 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. Our lab overrides the strict rules of nature governing protein synthesis and can tag our proteins with a variety of fluorine atoms replacing hydrogen. This provides us with a specific probe to study our proteins without background signals. Fluorine is an extremely sensitive probe, making it easy to observe as well as highly responsive to changes in its environment. Because we can understand the surroundings of each fluorine tag, we can define not only if a molecule binds to a protein, but where, and can rapidly quantify the strength of the interaction in cells and even whole organisms using 19F MRI. This specificity allows us to determine how the molecule in question disrupts the communication between the important protein partners and informs our use of chemistry to design new molecules. One particular area of biology we anticipate our methods will impact is the field of Epigenetics, which can be read about on our lab webpage.
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