Glycoconjugates

Glycoconjugates are biomolecules comprising carbohydrate moieties covalently attached to proteins, lipids or other scaffolds. They encompass glycoproteins, glycolipids and proteoglycans, and orchestrate fundamental processes in cell–cell communication, immune recognition and molecular trafficking. Structural diversity arises from variations in monosaccharide composition, linkage regiochemistry and stereochemistry, and branching, yielding thousands of distinct glycan sequences. Biosynthesis proceeds via enzyme-mediated glycosyl transfer and processing in the endoplasmic reticulum and Golgi apparatus, while chemical and chemoenzymatic methodologies enable access to defined structures. Characterisation integrates mass spectrometry, nuclear magnetic resonance spectroscopy and glycan microarrays to map glycosylation patterns and binding specificities. Advances in synthetic strategies and analytical technologies have propelled applications in vaccine design, targeted drug delivery and biomaterial engineering, underscoring the global relevance of glycoconjugate research in health and disease.

Research from Nature Portfolio

A dehydroxylative radical strategy has been developed to construct N-glycosylated heterocycles directly from stable 1-hydroxy sugars. Utilising copper-based metallaphotoredox catalysis under mild, aqueous-tolerant conditions, this approach achieves high stereoselectivity and site-selectivity across diverse substrates and permits late-stage functionalisation of pharmaceutical compounds. In a separate advance, a highly convergent preactivation-based one-pot glycosylation protocol has been applied to assemble a 92-mer mycobacterial arabinogalactan polysaccharide. By coupling large oligosaccharide fragments in a single operation, this work overcomes efficiency barriers in polysaccharide synthesis and sets a new benchmark for constructing long, branched carbohydrate chains with precise structural definition.

Research from all publishers

Innovations in promoter selection and protecting-group design have significantly improved stereocontrol and predictability in glycoside and oligosaccharide synthesis, facilitating access to both 1,2-cis and 1,2-trans linkages. An on-chip laser-assisted chemical-vapour glycosylation method enables parallel in situ assembly of glycan microarrays under inert, low-temperature conditions, streamlining the high-throughput screening of carbohydrate–protein interactions. In vaccine research, synthetic glycoconjugate vaccines constructed by precise conjugation of chemically synthesised oligosaccharides to carrier proteins have elucidated structure–immunogenicity relationships and yielded fully synthetic candidates that mimic bacterial surface antigens with enhanced purity and consistency.

Glycoconjugates publication trend

The graph below shows the total number of articles in glycoconjugates across all publications each year (not limited to Nature Index journals).

Technical terms

Glycoconjugate: A molecule formed by the covalent linkage of one or more carbohydrate chains to a protein, lipid or other scaffold.

Metallaphotoredox catalysis: A dual-catalyst method combining metal catalysis with photoredox activation under light irradiation to generate reactive intermediates.

One-pot glycosylation: A synthetic protocol in which multiple glycosylation steps are performed sequentially in a single reaction vessel without intermediate purification.

Glycan microarray: A platform that immobilises diverse carbohydrate structures on a surface for high-throughput binding studies with proteins or cells.

Preactivation-based synthesis: A glycosylation strategy in which sugar donors are preactivated to enhance coupling efficiency and selectivity prior to acceptor addition.

References

1. Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis. Nature Communications (2024).
2. Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units. Nature Communications (2017).
3. Advances in glycoside and oligosaccharide synthesis. Chemical Society Reviews (2023).
4. VaporLIFT: On‐Chip Chemical Synthesis of Glycan Microarrays. Advanced Functional Materials (2024).
5. Discovery of Semi- and Fully-Synthetic Carbohydrate Vaccines Against Bacterial Infections Using a Medicinal Chemistry Approach. Chemical Reviews (2021).