Chemoenzymatic Synthesis of Unnatural Nucleotide Sugars
for Enzymatic Bioorthogonal Labeling
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Abstract
In recent years, the development
of the enzymatic bioorthogonal
labeling strategy has offered exciting possibilities in the probing
of structure-defined glycan epitopes. This strategy takes advantage
of relaxed donor specificity and strict acceptor specificity of glycosyltransferases
to label target glycan epitopes with bioorthogonal reactive groups
carried by unnatural nucleotide sugars in vitro. The subsequent covalent
conjugation by bioorthogonal chemical reactions with either fluorescent
or affinity tags allows further visualization, quantification, or
enrichment of target glycan epitopes. However, the application and
development of the enzymatic labeling strategy have been hindered
due to the limited availability of unnatural nucleotide sugars. Herein,
a platform that combines chemical synthesis and enzymatic synthesis
for the facile preparation of unnatural nucleotide sugars modified
with diverse bioorthogonal reactive groups is described. By this platform,
a total of 25 UDP-GlcNAc and UDP-GalNAc derivatives, including the
most well explored bioorthogonal functional groups, were successfully
synthesized. Furthermore, the potential application of these compounds
for use in enzymatic bioorthogonal labeling reactions was also evaluated