Despite the ubiquity and importance of glycans in biology, methods to probe their structures in cells are limited. Strategies for studying other biomacromolecules, such as proteins, often exploit chemoselective reactions for covalent modification, capture, or imaging. Unlike amino acids that constitute proteins, glycan building blocks lack distinguishing reactivity because they are composed primarily of polyol isomers. Moreover, encoding glycan variants through genetic manipulation is complex. Therefore, we formulated a new, generalizable strategy for chemoselective glycan modification that directly takes advantage of cellular glycosyltransferases. Many of these enzymes are selective for the products they generate yet promiscuous in their donor preferences. Thus, we designed reagents with bioorthogonal handles that function as glycosyltransferase substrate surrogates. We validated the feasibility of this approach by synthesizing and testing probes of D-arabinofuranose (D-Ara<i>f</i>), a monosaccharide found in bacteria and an essential component of the cell wall that protects mycobacteria, including <i>Mycobacterium tuberculosis</i>. The result is the first probe capable of selectively labeling arabinofuranose-containing glycans. Our platform is now being expanded for developing new chemoselective labeling agents for other privileged monosaccharides including mannose which can target different glycans on the cell surface.

Biosynthetic glycan labeling

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.