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A comprehensive molecular understanding of carbohydrate aggregation is key to optimize carbohydrate utilization and to engineer bioinspired analogues with tailored shapes and properties. However, the lack of well‐defined synthetic standards has substantially hampered advances in this field. Herein, we employ a phosphorylation‐assisted strategy to synthesize previously inaccessible long oligomers of cellulose, chitin, and xylan. These oligomers were subjected to enzyme‐triggered assembly (ETA) for the on‐demand formation of well‐defined carbohydrate nanomaterials, including elongated platelets, helical bundles, and hexagonal particles. Cryo‐electron microscopy and electron diffraction analysis provided molecular insights into the aggregation behavior of these oligosaccharides, establishing a direct connection between the resulting morphologies and the oligosaccharide primary sequence. Our findings demonstrate that ETA is a powerful approach to elucidate the intrinsic aggregation behavior of carbohydrates in nature. Moreover, the ability to access a diverse array of morphologies, expanded with a non‐natural sequence, underscores the potential of ETA, coupled with sequence design, as a robust tool for accessing programmable glycan architectures. [ABSTRACT FROM AUTHOR]

Mucus is a complex biological hydrogel that acts as a barrier for almost everything entering or exiting the body. It is therefore of emerging interest for biomedical and pharmaceutical applications. Besides water, the most abundant components are the large and densely glycosylated mucins, glycoproteins of up to 20 MDa and carbohydrate content of up to 80 wt%. Here, we designed and explored a library of glycosylated peptides to deconstruct the complexity of mucus. Using the well‐characterized hFF03 coiled‐coil system as a hydrogel‐forming peptide scaffold, we systematically probed the contribution of single glycans to the secondary structure as well as the formation and viscoelastic properties of the resulting hydrogels. We show that glycan‐decoration does not affect α‐helix and coiled‐coil formation while it alters gel stiffness. By using oscillatory macrorheology, dynamic light scattering microrheology, and fluorescence lifetime‐based nanorheology, we characterized the glycopeptide materials over several length scales. Molecular simulations revealed that the glycosylated linker may extend into the solvent, but more frequently interacts with the peptide, thereby likely modifying the stability of the self‐assembled fibers. This systematic study highlights the interplay between glycan structure and hydrogel properties and may guide the development of synthetic mucus mimetics. [ABSTRACT FROM AUTHOR]

Solid-phase glycan synthesis (SPGS) is a valuable approach to access broad collections of complex, well-defined oligo- and polysaccharides in short amounts of time. The target structure is assembled following iterative cycles of glycosylation and deprotection, often aided by automated machines. To expand the scope of SPGS, new solid supports, linkers, glycosylation and deprotection reactions, and functionalization strategies are constantly being developed. Here we discuss the state of the art of SPGS, with particular focus on the chemistry happening on solid-phase. We highlight recent achievements as well as challenges to be addressed to expand the scope of SPGS even further. 1 Introduction 2 Solid-Phase Glycan Synthesis 2.1 The Solid Support 2.2 The Linker 2.3 The Assembly Process 2.4 Post-Assembly Manipulations 2.5 The Analysis 2.6 Cleavage from the Solid Support 3 Conclusion and Outlook [ABSTRACT FROM AUTHOR]

Scanning probe microscopy (SPM), in particular at low temperature (LT) under ultra-high vacuum (UHV) conditions, offers the possibility of real-space imaging with resolution reaching the atomic level. However, its potential for the analysis of complex biological molecules has been hampered by requirements imposed by sample preparation. Transferring molecules onto surfaces in UHV is typically accomplished by thermal sublimation in vacuum. This approach however is limited by the thermal stability of the molecules, i. e. not possible for biological molecules with low vapour pressure. Bypassing this limitation, electrospray ionisation offers an alternative method to transfer molecules from solution to the gas-phase as intact molecular ions. In soft-landing electrospray ion beam deposition (ESIBD), these molecular ions are subsequently mass-selected and gently landed on surfaces which permits large and thermally fragile molecules to be analyzed by LT-UHV SPM. In this concept, we discuss how ESIBD+SPM prepares samples of complex biological molecules at a surface, offering controls of the molecular structural integrity, three-dimensional shape, and purity. These achievements unlock the analytical potential of SPM which is showcased by imaging proteins, peptides, DNA, glycans, and conjugates of these molecules, revealing details of their connectivity, conformation, and interaction that could not be accessed by any other technique., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Carbohydrates are the most abundant organic material on Earth and the structural "material of choice" in many living systems. Nevertheless, design and engineering of synthetic carbohydrate materials presently lag behind that for protein and nucleic acids. Bottom-up engineering of carbohydrate materials demands an atomic-level understanding of their molecular structures and interactions in condensed phases. Here, high-resolution scanning tunneling microscopy (STM) is used to visualize at submolecular resolution the three-dimensional structure of cellulose oligomers assembled on Au(1111) and the interactions that drive their assembly. The STM imaging, supported by ab initio calculations, reveals the orientation of all glycosidic bonds and pyranose rings in the oligomers, as well as details of intermolecular interactions between the oligomers. By comparing the assembly of D- and L-oligomers, these interactions are shown to be enantioselective, capable of driving spontaneous enantioseparation of cellulose chains from its unnatural enantiomer and promoting the formation of engineered carbohydrate assemblies in the condensed phases., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)