ABSTRACT
The discovery of effective ligands for DC-SIGN receptor is one of the most challenging concepts of antiviral drug design due to the importance of this C-type lectin in infection processes. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides but glycosidic linkages are accessible to both chemical and enzymatic degradations. To avoid this problem, the synthesis of stable glycoside mimetics has attracted increasing attention. In this work we establish for the first time mono- and divalent C-glycosides based on d-manno and l-fuco configurations as prospective DC-SIGN ligands. In particular, the l-fucose glycomimetics were more active than the respective d-mannose ones. The highest affinity was assessed for simple 1,4-bis(α-l-fucopyranosyl)butane (SPR: IC50 0.43 mM) that displayed about twice higher activity than natural ligand Lex. Our results make C-glycosides attractive candidates for multivalent presentations.
Subject(s)
Cell Adhesion Molecules/metabolism , Glycosides/chemical synthesis , Lectins, C-Type/metabolism , Receptors, Cell Surface/metabolism , Biomimetics , Cell Adhesion Molecules/chemistry , Fucose/chemistry , Glycosides/chemistry , Humans , Lectins, C-Type/chemistry , Mannose/chemistry , Molecular Structure , Receptors, Cell Surface/chemistryABSTRACT
An approach to stereoselective synthesis of alpha- or beta-3-C-glycosylated L- or D-1,2-glucals starting from the corresponding alpha- or beta-glycopyranosylethanals is described. The key step of the approach is the stereoselective cycloaddition of chiral vinyl ethers derived from both enantiomers of mandelic acid. The preparation of 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosyl)methyl]-L-arabino-hex-1-enitol, 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosyl)methyl]-D-arabino-hex-1-enitol, and 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)methyl]-D-arabino-hex-1-enitol serves as an example of this approach.
Subject(s)
Disaccharides/chemical synthesis , Glycosylation , Mandelic Acids/chemistry , Stereoisomerism , Vinyl Compounds/chemistryABSTRACT
New types of porphyrin derivatives bearing "C-glycoside" moieties, either in 5,10,15,20- or in 5,15-meso-positions, were prepared and fully characterized. The presence of the glycosidic groups imparts to the title macrocycles, besides an amphiphilic character, a clear tendency to form chiral suprastructures upon solvent-driven self-aggregation in different aqueous-organic solvent mixtures. Supra-assembly phenomena, in terms of the size and morphology of the resulting structures, as well as their kinetics of aggregation, were studied by UV-visible, fluorescence, resonance light scattering (RLS), and CD spectroscopy, indicating that the morphology of the aggregates depends strongly on the structure of the porphyrin rings, and on the bulk conditions of aggregation.
