Gold Reagents for Protein-Polymer Conjugate Synthesis

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In this project funded by the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Professors Heather Maynard, Alexander Spokoyn, and Kendall Houk of the Department of Chemistry and Biochemistry at University of California-Los Angeles are developing gold chemistries to attach the strands of artificial polymers to naturally occurring proteins and peptides. The attachment of synthetic polymers to proteins and peptides create desirable properties in the biomolecules. Applications of these novel biomaterials include use as therapeutic agents with improved stability or solubility. This project has the potential to advance knowledge for commercial healthcare applications. The broader impacts of this research include increasing the number of students, particularly female and underrepresented minorities, with doctoral degrees in chemistry. Other efforts include outreach to girls by working with the Los Angeles Brownie and Junior Girl Scout Troops and the development of a program for Girl Scouts called Curieosity. Girls already interested in STEM are provided with mentorship and networking opportunities through the Mayor of Los Angeles’ program WiSTEM.This research is focused on developing gold reagents to synthesize polymer-protein conjugates. Organometallic gold(III) reagents are optimized using a combination of theory and experiment to understand the mechanism of cysteine arylation. Ligand design expands the use of these operationally-simple organometallic reagents in the synthesis of protein-polymer conjugates in aqueous solutions. These reactions are carried out by synthesizing protein and peptide-polymer conjugates by both “grafting to” and “grafting from” methods. Furthermore, non-native amino acid genetic encoding techniques are examined to place gold reagents at the protein surface for further modification with thiol-end-functionalized polymers. This research has the potential to develop new and highly efficient synthetic methodologies to prepare polymer-protein conjugates.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.