Work

Synthesis of sialylated human milk oligosaccharides by automated glycan assembly

Year: 2026

Type: article

Abstract: Sialic acids cap the ends of many glycan chains and play pivotal roles in cell signaling, immunity, and pathogen interactions. However, the fast synthesis of sialylated glycans by automated glycan assembly (AGA) has remained a long-standing challenge. Here we show a general strategy that leverages macrobicyclic sialic acid building blocks to achieve reliable α(2,3)- and α(2,6)-sialylation on solid support. Using this method, a collection of nine sialylated human milk oligosaccharides (HMOs) is assembled, including fucosyldisialyllacto-N-tetraose (DSLNF II), a highly branched, fucosylated structure that is very difficult to synthesize by solution-phase methods. An improved global deprotection protocol provides access to pure, functionalized complex glycans suitable for further biological studies. This work provides the broadly applicable solution for automated chemical sialylation, opening the door to prepare collections of sialylated glycans for biomedical research.

Source: Nature Communications

DOI: 10.1038/s41467-026-73028-w

Authors: Yan-Ting Kuo, Kim Le Mai Hoang, Peter H. Seeberger

Institutions: Max Planck Institute of Colloids and Interfaces, Freie Universität Berlin

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: European Commission, Max-Planck-Gesellschaft