NSF Award
2446734
With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Professor Kate Carroll from the University of Florida will investigate post-translational protein cysteine modifications. Cysteine plays essential roles in protecting the cell from oxidative damage through its thiol functional group. The importance of thiol modifications has been recognized by chemists and biologists alike, however, their impact on the chemical reactivity of sulfur has not been systematically studied until now. Through synthesis and physical-organic characterization, Dr. Carroll’s research explores how different cysteinyl thiol group modifications endow the sulfur atom with distinct chemical properties. This research will allow graduate students to gain specialized training in organosulfur chemistry and effective protein bioconjugation strategies. This project will also be integrated into an outreach program to introduce high school and undergraduate students to the science of bioorthogonal reactions.<br/><br/>This research project seeks to expand the fundamental science of electrophilic sulfur chemistry. The reactivity of electrophilic sulfur species are being investigated by kinetic and thermodynamic evaluation of models using time-resolved nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Reactivity is to be studied by generating small molecule models using advanced methods and new reactions in organosulfur chemistry. A range of post-translational thiol modifications identified as central to reversible redox regulation in biology are being targeted for study. The sulfur-based functionalities to be studied include cyclic sulfenamides, polarized disulfides, and S-sulfonates. Information gleaned from these studies is expected to provide both mechanistic guidance and new research tools in support of the investigation of protein cysteine oxidation-reduction chemistry in biology, particularly in dynamic redox environments.<br/><br/>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.
