In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

During the last decade there has been a growing interest in glycoimmunology, a relatively new research field dealing with the specific interactions of carbohydrates with the immune system. Pathogens’ cell surfaces are covered by a thick layer of oligo- and polysaccharides that are crucial virulence factors, as they mediate receptors binding on host cells for initial adhesion and organism invasion. Since in most cases these saccharide structures are uniquely exposed on the pathogen surface, they represent attractive targets for vaccine design. Polysaccharides isolated from cell walls of microorganisms and chemically conjugated to immunogenic proteins have been used as antigens for vaccine development for a range of infectious diseases. However, several challenges are associated with carbohydrate antigens purified from natural sources, such as their difficult characterization and heterogeneous composition. Consequently, glycoconjugates with chemically well-defined structures, that are able to confer highly reproducible biological properties and a better safety profile, are at the forefront of vaccine development. Following on from our previous review on the subject, in the present account we specifically focus on the most recent advances in the synthesis and preliminary immunological evaluation of next generation glycoconjugate vaccines designed to target bacterial and fungal infections that have been reported in the literature since 2011.

No abstract

Authors have been listed in alphabetical order. Sandra J. van Vliet and Barbara Richichi are co-last and co-corresponding authors.

In the search of molecules that could recognize sizeable areas of protein surfaces, a series of ten helical aromatic oligoamide foldamers was synthesized on solid phase. The foldamers comprise three to five monomers carrying various proteinogenic side chains, and exist as racemic mixtures of interconverting right-handed and left-handed helices. Functionalization of the foldamers by a nanomolar ligand of human carbonic anhydrase II (HCA) ensured that they would be held in close proximity to the protein surface. Foldamer-protein interactions were screened by circular dichroism (CD). One foldamer displayed intense CD bands indicating that a preferred helix handedness is induced upon interacting with the protein surface. The crystal structure of the complex between this foldamer and HCA could be resolved at 2.1 Å resolution and revealed a number of unanticipated protein-foldamer, foldamer-foldamer, and protein-protein interactions.