The quest for the construction of multivalent carbohydrate systems, with precise geometries that are highly efficient in interacting with carbohydrate binding proteins, has been a goal of synthetic chemists since the discovery of the multivalent nature of carbohydrate-mediated interactions. However, the control of the spatial and topological requirements for these systems is still a challenge. Glyconanoparticles (GNPs) are sugar-coated gold, iron oxide or semiconductor nanoparticles with defined thiol-ending glycosides that combine the multivalent presentation of carbohydrates (glycoclusters) with the special chemico-physical properties of the nano-sized metallic core. The possibility of attaching different types of carbohydrates and other molecules (such as luminescent probes, peptides, and magnetic chelates) onto the same gold nanoparticle in a controlled way (multifunctional GNPs), as well as modifying the core in order to obtain glyconanoparticles with magnetic or fluorescence properties (multimodal GNPs) makes this multivalent glyco-scaffold suitable for carrying out studies on carbohydrate-mediated interactions and applications in molecular imaging. In this review, we focus mainly on the rational design of glyconanoparticles as scaffolds for combining different ligands and survey the most recent examples of glyconanoparticles as both multivalent carbohydrate systems and probes for molecular imaging.

Coupling of capsular polysaccharides of pathogens to immunogenic protein carriers (conjugate vaccines) improves carbohydrate immune response. Our idea is to explore gold nanoclusters as carriers to prepare fully synthetic carbohydrate vaccines. Gold glyconanoparticles bearing a synthetic tetrasaccharide epitope related to the Streptococcus pneumoniae type 14 capsular polysaccharide (Pn14PS), the T-helper ovalbumin 323-339 peptide (OVA(323-339)), and D-glucose were prepared by a one-pot method. Their immunogenicity was tested in mice. Cytokine levels after spleen cell stimulation with OVA(323-339) were analyzed using a luminex-multiplex cytokine assay. The capacity of the evoked antibodies to promote the uptake of S. pneumoniae type 14 by leukocytes was assessed. Glyconanoparticles containing 45% of tetrasaccharide and 5% OVA(323-339) triggered specific anti-Pn14PS IgG antibodies. Cytokine levels confirmed that glyconanoparticles led to T-helper cell activation. The anti-saccharide antibodies promoted the phagocytosis of type 14 bacteria by human leukocytes, indicating the functionality of the antibodies. Gold nanoparticles have great potential as carriers for the development of a great diversity of fully synthetic carbohydrate-based vaccines.

Glycans are involved in various life processes and represent critical targets of biomedical developments. Nevertheless, the accessibility to long glycans with precise structures remains challenging. Here we report on the synthesis of glycans consisting of [→4)-α-Rha-(1 → 3)-β-Man-(1 → ] repeating unit, which are relevant to the O-antigen of Bacteroides vulgatus, a common component of gut microbiota. The optimal combination of assembly strategy, protecting group arrangement, and glycosylation reaction has enabled us to synthesize up to a 128-mer glycan. The synthetic glycans are accurately characterized by advanced NMR and MS approaches, the 3D structures are defined, and their potent binding activity with human DC-SIGN, a receptor associated with the gut lymphoid tissue, is disclosed.