CAREER: Secondary Amine Selective Petasis (SASP) Bioconjugation

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Monika Raj from Auburn University to develop a chemical method that can selectively label a specific site on a biomolecule in the presence of sea of other similar sites. In this case, the specifically labeled site is known to "turn on" or "turn off" very important functions inside the cell which are responsible for cell growth, as well as the transfer of information from one cell to another. The proposal aims to use the new chemical labeling method to better understand the biological significance of the reactive sites, that is how they control cellular function. Dr. Raj develops methods based on innovative applications of classical chemical reactions for visualizing biomolecules and tagging them with dye. This project also supports continued efforts toward increasing diversity in science fields by allowing graduate and undergraduate students from underrepresented minorities to gain training in both organic chemistry and biochemistry. Outreach activities engage high school students (especially women and underrepresented minorities) and expose them to basic concepts of science through fun experimentation, ultimately encouraging them to pursue studies and academic careers in STEM fields.Chemical strategies that can target a particular functional group at a single site in the presence of reactive amino acid side chains on protein surfaces are limited. Even more rare are organic reactions that can proceed under conditions mild enough to label biomolecules. To address these challenges, this research project develops a new multicomponent bioconjugation method based on the classical organic Petasis reaction for selective labeling of proteins containing secondary amines. This method is employed for labeling mono-methyl lysine containing posttranslational modifications (PTMs) on proteins with various cargoes. The dysregulation of these mono methyl lysine PTMs has been linked to a variety of different biological malfunctions, yet the chemical methods for selective detection of mono methyl lysine PTMs are still lacking. This research provides a highly selective chemical tool that can effectively detect mono methyl lysine PTMs which, are present not only on histone proteins but also on other proteins and dictate various protein-protein interactions and functions. Thus, the proposed research has a great potential to further our understanding of how these PTMs regulate various cellular signaling processes and how the PTMs themselves are regulated.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.