Modular SNO-OCT Scaffolds for Rapid, ‘Mutually Orthogonal’ Bioorthogonal Labeling

Dr.Jennifer M. Schomaker, Associate Professor, Department of Chemistry, University of Wisconsin-Madison
 Monday, March 15, 2021
 virtually at

Abstract: The importance of elucidating details of the function, dynamics, and interdependence of complex biological processes has driven the design of innovative new tools to study the behavior of cellular systems. Chemistry employed in biological systems requires close attention to reagent/product stabilities, biocompatibility, chemoselectivity, and the absence of non-specific labeling; due to these constraints, studying processes that occur inside cells remains challenging, especially when interrogating the behaviors of multiple biomolecules simultaneously in real time. Despite the breadth of current bioorthogonal probes, most are designed to examine a single biological event and may suffer from slow rates, poor chemoselectivity/off-target reactivities, or ineffective uptake that limits labeling to only the cell surface. This talk will discuss our development of an unusual class of heterocyclic alkynes, termed ‘SNO-OCTs’, where the polarizability of the triple bond is predictably tuned for mutually exclusive, 'orthogonal bioorthogonality' with diverse cycloaddition partners. A combination of synthetic, computational, and biological studies in collaboration with the Raines group sets the stage for use of SNO-OCTs in the labeling of single-chain antibody fragments and future study of the glycocalyx.

Biographical Sketch: Professor Schomaker began her research career at Dow Chemical in Organic Chemicals and Polymers, later moving to Agricultural Chemicals Process Research, where she participated in the route selection and scale-up campaigns for two new herbicides. She obtained her Ph.D. with Professor Babak Borhan at Michigan State University in 2006 before moving to UC-Berkeley as an NIH postdoctoral fellow in the labs of Professor Robert G. Bergman and F. Dean Toste. She began her independent career at the University of Wisconsin-Madison in 2009, where she is now a full professor. Research in the Schomaker group encompasses method development, catalysis, and total syntheses. Oxidative allene aminations enable flexible syntheses of amine 'triads' in structurally complex molecules with intriguing bioactivities, including jogyamycin and other molecules that target the ribosome. Unified strategies to construct diverse bioactive N-heterocycles are another area of current interest. In the context of catalyst design, the range of coordination geometries available to Ag(I) have been harnessed for tunable, chemo-, regio- and stereoselective group transfer reactions. Applications of synthetic methods to biological problems include collaborative investigations of heterocyclic alkynes with tunable polarizability to achieve mutually exclusive, bioorthogonal labeling reagents for both in vivo and in vitro use. Awards include the NSF-CAREER, Sloan Research Fellowship, Thieme Chemistry Journal Award, ACS-WCC Rising Star Award, MSU Distinguished Alumni Award, UW-Vilas Mid-Career Award, Kavli Fellow, and the Somojai Visiting Miller Professorship at UC-Berkeley.

If you have a disability and desire any assistive devices or services to participate in these research seminars, please contact Dr. Wenjun Du, 989-774-7568 or, during normal business hours to discuss accommodations ten days prior to each event.