About the Seminar
Covalent protein modification chemistries have become an essential component to a wide array of fields ranging from drug discovery and chemical biology to materials chemistry. As a result, the development of new bioconjugation chemistries with enhanced sophistication and new capabilities serve to not only enable access to protein conjugates with new functional properties, but can also provide unique lenses through which to probe biological structure and processes directly in situ. This seminar will discuss recent efforts by our group to develop chemical transformations that covalently modify biological matter via unusual or underexplored mechanistic pathways. We have identified three cationic, aromatic scaffolds that allow us to invoke three distinct mechanistic paradigms in protein modification: (1) N-substituted pyridinium salts for photo-induced electron transfer-driven tryptophan modification (2) cationic, aromatic sulfonate esters for ultra-rapid, radical photo de-caging of sulfonyl radicals and (3) cationic, aromatic acyl donors for selective protein acylation driven by non-covalent interactions. By invoking these unusual reaction mechanisms, we are able to access chemical modifications on traditionally non-reactive biological moieties with rapid kinetics and under biologically compatible conditions. This has enabled us to translate our chemistry directly from the flask to in situ for use as chemical probes to interrogate biomolecular structures in their native environment.
About the Speaker
Michael grew up in Salisbury, on the eastern shore of Maryland, and received his undergraduate degree from Salisbury University in 2006. There, he was an undergraduate researcher in Professor Elizabeth Papish’s group where he worked on the synthesis of small molecule-metal complexes designed to mimic metalloenzyme active sites. He then moved to the University of Delaware, where he pursued his Ph.D. in Professor Joseph Fox’s laboratory. His research in the Fox group focused on the development of new synthetic methods, the total synthesis of natural products, and the development of bio-orthogonal chemistry. After receiving his Ph.D. in Organic Chemistry in 2013, he moved to the United Kingdom to take up a post-doctoral position in the laboratory of Professor Matthew Gaunt at the University of Cambridge, where he was awarded a Marie Curie Postdoctoral Fellowship in 2014. His research at Cambridge primarily focused on the development of a non-classical reactive platform for the selective chemical modification of proteins. In August of 2017, Michael moved back across the pond to take up his position in the Chemistry Department at the University of Wyoming. Michael’s research program is underpinned by an interest in developing organic transformations for use at the chemistry-biology interface. During his time at Wyoming, Michael has received an NSF CAREER award, a Thieme Chemistry Journals award, and an NIH outstanding investigator award.
