J Am Chem Soc. 2026 Jun 22. doi: 10.1021/jacs.6c06320. Online ahead of print.

ABSTRACT

Glycoproteins often exist in nature as heterogeneous glycoforms, making it difficult to obtain pure homogeneous samples for studying the roles of specific N-glycans within a glycoprotein. Despite various chemical and enzymatic methods developed for the synthesis of N-glycans, access to highly diverse N-glycans remains a challenge. Herein, we report a concise strategy for the synthesis of multiantennary N-glycans from designed common core structures with phosphate and sulfate protecting groups, which can be selectively deprotected by respective phosphatase and sulfatase, thereby enabling enzymatic elongation to install a desired glycan chain at a specific antenna. We also explored the directing effect of galactose sulfation for enzymatic fucosylation of the neighboring GlcNAc, further expanding the structural diversity of multiantennary N-glycans. Starting from sulfate and phosphate-terminated core structures, this synthetic strategy in aqueous solution provides an efficient and practical route for the enzymatic assembly of a diverse array of complex N-glycans for biological study.

PMID:42329121 | DOI:10.1021/jacs.6c06320