The Flexibility of Oligosaccharides Unveiled Through Residual Dipolar Coupling Analysis

The intrinsic flexibility of glycans complicates the study of their structures and dynamics, which are often important for their biological function. NMR has provided insights into the conformational, dynamic and recognition features of glycans, but suffers from severe chemical shift degeneracy. We employed labelled glycans to explore the conformational behaviour of a β(1-6)-Glc hexasaccharide model through residual dipolar couplings (RDCs). RDC delivered information on the relative orientation of specific residues along the glycan chain and provided experimental clues for the existence of certain geometries. The use of two different aligning media demonstrated the adaptability of flexible oligosaccharide structures to different environments

Supramolecular Assembly and Chirality of Synthetic Carbohydrate Materials

Hierarchical carbohydrate architectures serve multiple roles in nature. Hardly any correlations between the carbohydrate chemical structures and the material properties are available due to the lack of standards and suitable analytic techniques. Therefore, designer carbohydrate materials remain highly unexplored, as compared to peptides and nucleic acids. A synthetic D‐glucose disaccharide, DD, was chosen as a model to explore carbohydrate materials. Microcrystal electron diffraction (MicroED), optimized for oligosaccharides, revealed that DD assembled into highly crystalline left‐handed helical fibers. The supramolecular architecture was correlated to the local crystal organization, allowing for the design of the enantiomeric right‐handed fibers, based on the L‐glucose disaccharide, LL, or flat lamellae, based on the racemic mixture. Tunable morphologies and mechanical properties suggest the potential of carbohydrate materials for nanotechnology applications

Systematic Hydrogen‐Bond Manipulations To Establish Polysaccharide Structure–Property Correlations

A dense hydrogen‐bond network is responsible for the mechanical and structural properties of polysaccharides. Random derivatization alters the properties of the bulk material by disrupting the hydrogen bonds, but obstructs detailed structure–function correlations. We have prepared well‐defined unnatural oligosaccharides including methylated, deoxygenated, deoxyfluorinated, as well as carboxymethylated cellulose and chitin analogues with full control over the degree and pattern of substitution. Molecular dynamics simulations and crystallographic analysis show how distinct hydrogen‐bond modifications drastically affect the solubility, aggregation behavior, and crystallinity of carbohydrate materials. This systematic approach to establishing detailed structure–property correlations will guide the synthesis of novel, tailor‐made carbohydrate materials

Systematic Hydrogen‐Bond Manipulations To Establish Polysaccharide Structure–Property Correlations

A dense hydrogen‐bond network is responsible for the mechanical and structural properties of polysaccharides. Random derivatization alters the properties of the bulk material by disrupting the hydrogen bonds, but obstructs detailed structure–function correlations. We have prepared well‐defined unnatural oligosaccharides including methylated, deoxygenated, deoxyfluorinated, as well as carboxymethylated cellulose and chitin analogues with full control over the degree and pattern of substitution. Molecular dynamics simulations and crystallographic analysis show how distinct hydrogen‐bond modifications drastically affect the solubility, aggregation behavior, and crystallinity of carbohydrate materials. This systematic approach to establishing detailed structure–property correlations will guide the synthesis of novel, tailor‐made carbohydrate materials

Phosphates as Assisting Groups in Glycan Synthesis

In nature, phosphates are added to and cleaved from molecules to direct biological pathways. The concept was adapted to overcome limitations in the chemical synthesis of complex oligosaccharides. Phosphates were chemically placed on synthetic glycans to ensure site-specific enzymatic elongation by sialylation. In addition, the deliberate placement of phosphates helped to solubilize and isolate aggregating glycans. Upon traceless removal of the phosphates by enzymatic treatment with alkaline phosphatase, the native glycan structure was revealed, and the assembly of glycan nanostructures was triggered

Systematic Structural Characterization of Chitooligosaccharides Enabled by Automated Glycan Assembly

Chitin, a polymer composed of beta(1-4)-linked N-acetyl-glucosamine monomers, and its partially deacetylated analogue chitosan, are abundant biopolymers with outstanding mechanical as well as elastic properties. Their degradation products, chitooligosaccharides (COS), can trigger the innate immune response in humans and plants. Both material and biological properties are dependent on polymer length, acetylation, as well as the pH. Without well-defined samples, a complete molecular description of these factors is still missing. Automated glycan assembly (AGA) enabled rapid access to synthetic well-defined COS. Chitin-cellulose hybrid oligomers were prepared as important tools for a systematic structural analysis. Intramolecular interactions, identified by molecular dynamics simulations and NMR analysis, underscore the importance of the chitosan amino group for the stabilization of specific geometries

Synthesis of a glycan hairpin

The primary sequence of a biopolymer encodes the essential information for folding, permitting to carry out sophisticated functions. Inspired by natural biopolymers, peptide and nucleic acid sequences have been designed to adopt particular three-dimensional (3D) shapes and programmed to exert specific functions. In contrast, synthetic glycans capable of autonomously folding into defined 3D conformations have so far not been explored owing to their structural complexity and lack of design rules. Here we generate a glycan that adopts a stable secondary structure not present in nature, a glycan hairpin, by combining natural glycan motifs, stabilized by a non-conventional hydrogen bond and hydrophobic interactions. Automated glycan assembly enabled rapid access to synthetic analogues, including site-specific 13C-labelled ones, for nuclear magnetic resonance conformational analysis. Long-range inter-residue nuclear Overhauser effects unequivocally confirmed the folded conformation of the synthetic glycan hairpin. The capacity to control the 3D shape across the pool of available monosaccharides has the potential to afford more foldamer scaffolds with programmable properties and functions

Deoxyfluorination tunes the aggregation of cellulose and chitin oligosaccharides and highlights the role of specific hydroxyl groups in the crystallization process

Cellulose and chitin are abundant structural polysaccharides exploited by nature in a large number of applications thanks to their crystallinity. Chemical modifications are commonly employed to tune polysaccharide physical and mechanical properties, but generate heterogeneous mixtures. Thus, the effect of such modifications is not well understood at the molecular level. In this work, we examined how deoxyfluorination (site and pattern) impact the solubility and aggregation of well-defined cellulose and chitin oligomers. While deoxyfluorination increased solubility in water and lowered the crystallinity of cellulose oligomers, chitin was much less affected by the modification. The OH/F substitution also highlighted the role of specific hydroxyl groups in the crystallization process. This work provides guidelines for the design of cellulose- and chitin-based materials. A similar approach can be imagined to prepare cellulose and chitin analogues capable of withstanding enzymatic degradation

Neighboring Group Participation of Benzoyl Protecting Groups in C3- and C6-Fluorinated Glucose

Fluorination is a potent method to modulate chemical properties of glycans. Here, we study how C3- and C6-fluorination of glucosyl building blocks influence the structure of the intermediate of the glycosylation reaction, the glycosyl cation. Using a combination of gas-phase infrared spectroscopy and first-principles theory, glycosyl cations generated from fluorinated and non-fluorinated monosaccharides are structurally characterized. The results indicate that neighboring group participation of the C2-benzoyl protecting group is the dominant structural motif for all building blocks, correlating with the β-selectivity observed in glycosylation reactions. The infrared signatures indicate that participation of the benzoyl group in enhanced by resonance effects. Participation of remote acyl groups such as Fmoc or benzyl on the other hand is unfavored. The introduction of the less bulky fluorine leads to a change in the conformation of the ring pucker, whereas the structure of the active dioxolenium site remains unchanged

Visualizing chiral interactions in carbohydrates adsorbed on Au(111) by high-resolution STM imaging

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