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A general stereospecific glycosylation is developed that is applicable across a range of monosaccharides. A directing-group-on-leaving-group strategy allows mild donor activation and enables the complete inversion of anomeric configuration with excellent yields. This method can be applied in multistep oligosaccharide syntheses and automated glycan assembly.

Human milk oligosaccharides (HMOs) have highly diverse and branched structures that present a significant challenge for chemical synthesis. Here, the author reports that masking the amino group in glucosamine with a p-nitrobenzyloxycarbonyl (pNZ) group enhances coupling and deprotection efficiency during the automated glycan assembly (AGA) of homogeneous HMOs.

Automated glycan assembly has proven a powerful method to rapidly synthesize large oligosaccharides, though stereoselective cis-glycosylation remains a challenge. Here, the authors demonstrate a system to selectively incorporate multiple cis-glycosidic linkages by use of remote participating groups.

The phosphoethanolamine modified cellulose in E. colibiofilms has revealed that polysaccharide functionalization alters the biofilm properties. Here, the authors show a model system to explore the role of phosphoethanolamine and other unnatural modifications on the properties of the biofilm-inspired assemblies.

The branched structure and stereoisomerism of carbohydrates make them difficult to analyse; here, ion mobility–mass spectrometry is used to distinguish unambiguously between synthetic trisaccharides that differ in connectivity or configuration.

Ready access to sugars in which the various hydroxyl groups are differentially protected will be of benefit in the production of vaccines, antibiotics and drugs. Here, a chemoenzymatic method that provides a direct route to such protected sugars is described.

An automated synthesis instrument comprising a series of continuous flow modules that are radially arranged around a central switching station can achieve both linear and convergent syntheses.

Glycosyl cations are key intermediates in glycosylation reactions, but their structure has remained elusive due to their transient nature. Here, the authors perform an in-depth structural analysis and report that C2-participating protective groups induce acetoxonium cations with distinct ring conformations.

Glycomics: like proteins and nucleic acids, carbohydrates have essential roles in the cell, but the tools to synthesize and analyse this third class of biopolymer have, until recently, lagged far behind.

An imaging method combining soft-landing electrospray ion beam deposition and low-temperature scanning tunnelling microscopy resolves the structures of glycans at sub-nanometre resolution, revealing the connectivity of glycan chains and the types of linkages.

Immunologically-active glycans are promising vaccine candidates but can be difficult to synthesize. Here, the authors show that pentavalent display of a minimal disaccharde epitope on a chemical scaffold can mimic a native C. difficileglycan antigen, representing a simple approach to synthetic vaccine production.

The photoelectrochemical performance of carbon nitride is still insufficient for organic transformations. Here, the authors introduce a spin coating strategy for the synthesis of carbon nitride photoelectrodes, enabling high yields in C-H functionalization.

A semisynthetic carbohydrate-lipid vaccine that combines a known adjuvant that has been used in disease models with a lipid capable of activating iNKT cells protects against Streptococcus pneumoniae infection in mice.

Reducing the manual labour associated with chemical synthesis by using continuous-flow reactors that not only make compounds, but also purify them, opens up new avenues to reaction automation and rapid scale-up.

Reducing the glycan heterogeneity of recombinant proteins may improve the efficacy of biopharmaceuticals.

Inspired by the design of peptide and nucleic acid sequences to adopt particular three-dimensional shapes, natural glycan motifs have now been combined to construct a glycan that adopts a hairpin conformation in water. Thus a designed glycan can now autonomously fold into a stable secondary structure absent in nature.

Although Tc toxins are a major class of bacterial toxin translocation systems, little is known about their receptor binding. Here, the authors identify heparins/heparan sulfates and Lewis antigens as receptors for different Tc toxins, determine cryo-EM structures of three toxin-glycan complexes and propose a two-step cell adhesion mechanism for Tc toxins.

The role of cationic intermediates in the benzylidene-directed synthesis of 1,2-cis glycosidic linkages is unclear. Now cryogenic infrared spectroscopy provides insight into the S_N1 mechanism of benzylidene-directed glycosylation reactions. The analysis reveals that cationic intermediates form anhydro cations through a two-step process, which correlates with the observed stereochemical outcome.

Fabrication of hybrid photoelectrodes on a subsecond timescale with low energy consumption remains a challenge. Here, the authors report a modular approach, laser-driven transfer synthesis, to build a library of structurally defined transition metal oxide composite films, enabling the creation of materials for diverse applications.

Artificial microswimmers can emulate the autonomous regulation of chemotactic motility of living organisms. Frank et al. realize a chemotactic locomotion of emulsion droplets, composed of two phase-separated fluids, that can be reversibly directed up or down a chemical concentration gradient.

PCSK9 interacts with LDL receptor, causing its degradation, and consequently reduces the clearance of LDL. Here, Gustafsen et al. show that PCSK9 interacts with heparan sulfate proteoglycans and this binding favors LDLR degradation. Pharmacological inhibition of this binding can be exploited as therapeutic intervention to lower LDL levels.

Understanding the structure and function of carbohydrates remains a key challenge for chemical biologists. Developments in carbohydrate synthesis and analysis together with the advent of high-throughput methods such as carbohydrate microarrays have helped shed light on the function of glycoconjugates. Similarly, consortia have provided technology platforms and focus to a burgeoning field. Now, recruitment of scientists from related fields and further integration of chemistry and biology to achieve technical goals are needed for rapid advancements.

Strains of methicillin-resistant Staphylococcus aureus use a prophage-encoded glycosyltransferase to alter the glycosylation of their wall teichoic acid and thereby evade antibody-mediated immune responses.

Carbohydrate–protein interactions are key for cell–cell and host–pathogen recognition, but their hydrophilic nature makes the development of drug-like inhibitors a challenge. Here, screening of fragment libraries identifies metal-binding pharmacophores as novel scaffolds for the inhibition of Ca²⁺-dependent carbohydrate–protein interactions.

The anticoagulant rivaroxaban is the first approved direct inhibitor of the serine protease factor Xa. This article presents the history of rivaroxaban's development, from its discovery to the preclinical and clinical studies, and also provides a brief overview of other oral anticoagulants in advanced clinical development.