The goal of this Competing Revision will be to extend the tools being developed in the R01 GM132460 to glycoscience applications in collaboration with carbohydrate chemical biologists Catherine Leimkuhler Grimes (UD) and Jennifer Kohler (UTSW). This Competing Revision will expand the toolkit being developed under the parent award to develop bioorthogonal N-acylmuramic acid (NAM) and N-acylglucosamine (NAG) molecules for use in probe applications in microbiology and immunology research. The technology to be developed will enable dramatically faster kinetics than is possible with current bioorthogonal methods for metabolic glycoengineering which generally require the prolonged incubation with labeling reagents at millimolar concentration. The Fox group will collaborate with Grimes and Kohler to develop a general platform for creating common intermediates that can be subjected to late-stage, catalytic cross-coupling or reduction to produce a variety of tetrazine-monosaccharide analogs for metabolic oligosaccaride engineering. The method will be applied to the NAM platform developed by collaborator Grimes and will be extended to the development of GlcNAc analogs developed by collaborator Kohler.
The goal of this Competing Revision will be to add a new specific aim that will extend the tools being developed in the R01 GM132460 to glycoscience applications in collaboration with carbohydrate chemical biologists Catherine Leimkuhler Grimes (UD) and Jennifer Kohler (UTSW). The work will result in advance new chemical tools for studying glycans in living systems that will be made broadly available to the glycoscience research community.