1,2‐Mannobioside Mimic: Synthesis, DC‐SIGN Interaction by NMR and Docking, and Antiviral Activity

Abstract

The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high interest because of the role played by this C-type lectin in immunity and infection processes. The low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. Herein, we present a good alternative for a DC-SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. NMR and docking studies have been performed to study the interaction of this mimic with DC-SIGN in solution demonstrating that this pseudomannobioside is a good ligand for this lectin. In vitro studies using an infection model with Ebola pseudotyped virus demonstrates that this compound presents an antiviral activity even better than the corresponding disaccharide and could be an interesting ligand to prepare multivalent systems with higher affinities for DC-SIGN with potential biomedical applications.

Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

“…They both contain a terminal mannose residue connected to a conformationally locked cyclohexanediol [67] that mimics a mannose unit -α-1,2-substituted. Both 30 and 31 bind to the Ca ++ ion in DC-SIGN binding site using the non-reducing end residue (X-ray: [68,69]), inhibit DC-SIGN binding to mannosylated BSA [70], display a measurable selectivity [68,71] against Langerin, are not cyototoxic and are active in the Ebola infection model.…”

Glycodendritic structures: tools to interact with DC-SIGN

“…A pseudo-1,2-mannobioside 1 (Figure 6), which contains a mannose unit connected to a conformationally locked cyclohexanediol to mimic 1,2-mannobioside (Mana (1,2)Man) (Reina et al, 2007). The pseudo-trisaccharide 2 mimicking the linear Mana (1,2)Mana (1,6)Man trisaccharide of the D3 arm of Man 9 , (Figure 6) was designed following the same concept .…”

DC-SIGN Antagonists – A Paradigm of C-Type Lectin Binding Inhibition

“…DC-SIGN antagonists work by inhibiting pathogen interaction with DC-SIGN, so the very first phase of pathogen infection can be inhibited, as proven in in vitro experiments [10,41,42]. DC-SIGN antagonists may be designed as monovalent glycomimetics based on the DC-SIGN-binding oligosaccharides and their multimeric presentation [43].…”

“…The most extensive work regarding the choice of the monosaccharide unit comes from the work of Bernardi and Rojo's groups from CARMUSYS [41,50,57]. In particular, they have shown that L-fucose can be incorporated in glycomimetic surrogates of Lewis-X trisaccharide to obtain even better affinity than the native trisaccharide.…”