Bioorthogonal and Photoswitchable Tools for Protein Control

I have utilized key tools in chemical biology research, namely bioorthogonal chemistry, genetic code expansion, and targeted protein degradation to investigate new ways to impart specific and selective control over protein function. I have developed and optimized a new tool for in cellulo protein bioconjugation quantification using simple western blotting techniques (Chapter 1.0) and site-specifically recruited bioorthogonally modified E3 ligase ligands to proteins with an expanded genetic code for investigation of protein degradability (Chapter 2.0). Expanding on these methods, I have also imparted optical control of site-specific degradation via photocaged, bioorthogonal E3 ligase ligands (Chapter 3.0) and developed a tool for the investigation of hydrophobic degradation through bioconjugation of two hydrophobic ligands (Chapter 4.0). In addition to my extensive work in conjugating various ligands to proteins with expanded genetic codes and investigating the resultant impact on protein expression, I have also utilized photoswitchable molecules to impart reversible optical control over proteins and peptides. We developed the best photoswitchable amino acid to date and utilized it to impart optical control over protein translation (Chapter 6.0). I have also developed a series of fluorinated azobenzene chromophores for rigid stapling and reversible isomerization of strategically designed peptides (Chapter 7.0), and fluorinated unnatural amino acids for photocontrol over protein structure and resultant function in biological systems (Chapter 8.0).