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Biosynthetic Glycan Labeling
Name
2021.07.01.450741v1.full.pdf
Description
Submitted version
Size
1.16 MB
Format
Adobe PDF
Checksum (MD5)
24d0df2163abb31ed0693503e84ea209
Author(s)
Marando, Victoria M
Kim, Daria E
Calabretta, Phillip J
Kraft, Matthew B
Bryson, Bryan D
Kiessling, Laura L
Date Issued
2021
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Marando, Victoria M, Kim, Daria E, Calabretta, Phillip J, Kraft, Matthew B, Bryson, Bryan D et al. 2021. "Biosynthetic Glycan Labeling." Journal of the American Chemical Society, 143 (40).
Version
Original manuscript
Abstract
Glycans are ubiquitous and play important biological roles, yet chemical methods for probing their structure and function within cells remain 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-Araf), a monosaccharide found in bacteria and an essential component of the cell wall that protects mycobacteria, including Mycobacterium tuberculosis. The result is the first probe capable of selectively labeling arabinofuranose-containing glycans. Our studies serve as a platform for developing new chemoselective labeling agents for other privileged monosaccharides. This probe revealed an asymmetric distribution of d-Araf residues during mycobacterial cell growth and could be used to detect mycobacteria in THP1-derived macrophages.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
10.1021/JACS.1C07430
