Addressing the scope of the azide-nitrile cycloaddition in glycoconjugate chemistry. The assembly of C-glycoclusters on a calix[4]arene scaffold through tetrazole spacers

New glycoclusters constituted of ribosylmethyl, galactosylmethyl, and glucosylmethyl fragments assembled on a calix[4]arene platform by means of propoxytetrazole spacers have been prepared by coupling the corresponding sugar azides with p-toluenesulfonyl cyanide, and then reacting 1-glycosylmethyl-5-sulfonyl-tetrazole derivatives thus formed with a calix[4]arene tetrol.     

Synthesis of structure-defined branched hyaluronan tetrasaccharide glycoclusters

Hyaluronan is a glycosaminoglycan with a large number of biological activity. Hyaluronan of different molecular weight often shows different biological activity, sometimes even completely opposite, but the mechanism is not clear. Herein, the hyaluronan tetrasaccharide glycoclusters using hyaluronan tetrasaccharide obtained by enzymolysis of natural hyaluronan were firstly synthesized in high yield. The structurally determined and diverse glycoclusters were of wide molecular weight range and might be used for mimicking the biological activity of natural hyaluronan and facilitating the mechanism study.     

Glycoclusters presenting lactose on calix[4]arene cores display trypanocidal activity

A new series of water-soluble tetravalent glycoclusters incorporating β-lactosyl residues attached to a central calix[4]arene core was synthesised using azide-alkyne Cu(I)-catalysed cycloaddition (‘click chemistry’). Carbohydrate moieties were attached either to the upper or lower rim of rigid cone-shaped or partial cone macrocycles via 14-21 atom spacer arms. The glycoclusters with a C₄-symmetrical arrangement of β-lactosyl residues showed trypanocidal activity, with one of them showing comparable activity to established anti-trypanosomal drug benznidazole in in vitro anti-parasite assays.     

Synthesis and lectin-binding activity of luminescent silica particles peripherally functionalized with lactose

A novel O-protected lactose (Galβ1→4Glcβ1-) derivative bearing trimethoxysilyl group at the aglycon was developed as a silane coupling agent. Reaction of the coupling agent with tris(2,2′-bipyridine)ruthenium (II) dichloride (Rubpy) doped silica particle gave a Rubpy-doped silica particle peripherally functionalized with O-protected lactose derivative. De-O-protection of the particle with aqueous ammonia provided lactose-coating Rubpy-doped silica particles, combining luminophor encapsulated in silica matrix and carbohydrate having lectin-recognition ability. Specific adhesion of fluorescein isothiocyanate-labeled peanut agglutinin (FITC-PNA) to the lactose-coating Rubpy-doped silica particles was confirmed by fluorescence microscopic analysis.     

Highly luminescent glycocluster: silole-core carbosilane dendrimer having peripheral globotriaose

A novel glycocluster periphery functionalized by globotriaose (Galα1-4Galβ1-4Glcβ1-) possessing a silole moiety as a luminophor was synthesized. The photoluminescence spectrum of the glycocluster in pure water showed extremely strong emission at 475 nm. Analogous intense emission of the silole dendrimer was also observed in a lower water fraction of water/acetone mixture. The water fraction of the silole dendrimer solution strongly affected the emission intensity; however, these luminescences were constantly detected at around 475 nm.     

Synthesis of carbosilane dendrimers having peripheral mannose and mannobiose

The mannose monosaccharide derivative, acetylthiopropyl 2,3,4,6-tetra-O-acetyl-α-d-mannopyranoside (Man), and the mannobiose derivative, acetylthiopropyl 2,4,6-tri-O-acetyl-3-O-(2′,3′,4′,6′-tetra-O-acetyl-α-d-mannopyranosyl)-α-d-mannopyranoside (α-1,3-Man), were synthesized respectively. These mannose derivatives were introduced into carbosilane dendrimer scaffolds of the zero and first generations. As a result, six carbosilane dendrimers were functionalized by Man and α-1,3-Man. Isothermal titration microcalorimetry was done to determine binding assay between mannose moieties of carbosilane dendrimer and concanavalin A. It was found that carbosilane dendrimers bound more efficiently to concanavalin A than free mannose (Me-α-Man) and mannobiose (Me-α-1,3-Man).     

Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using β-cyclodextrin as a key scaffold material

An efficient and practical method for the large-scale synthesis of an anti-inflammatory glycocluster having seven sialyl Lewis X (SLeX) residues was established on the basis of chemical and enzymatic strategy from β-cyclodextrin (β-CD) as a key starting scaffold material. A key intermediate, β-CD derivative having seven N-acetyl-d-glucosamine (GlcNAc) residues [(GlcNAc)₇CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-β-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)₇CD proceeded smoothly by means of β-1,4-galactosyltransferase, α-2,3-sialyltransferase, and α-1,3-fucosyltransferase V in the presence of the corresponding sugar nucleotides (UDP-Gal, CMP-Neu5Ac, and GDP-Fuc) and allowed to give a mono-dispersed glycodendrimer (M_w=7924.5, calcd for C₃₀₁H₄₉₀N₂₁O₁₉₆S₇Na₇; MALDI-TOF MS, m/z 7946 [M+Na]⁺) that completely substituted with seven SLeX branches at C-6 positions in excellent overall yield (74%, 3 steps). Hyper-branched glycodendrimer, (SLeX)₇CD, exhibited highly amplified inhibitory effect on the interaction of E-selectin with SLeXn-BSA immobilized on the sensor chip by means of surface plasmon resonance method.     

Fluorescence quenching detection of peanut agglutinin based on photoluminescent silole-core carbosilane dendrimer peripherally functionalized with lactose

A glycocluster peripherally functionalized with a lactose (Lac: Galβ1→4Glcβ1–) derivative possessing a silole moiety as a luminophore was synthesized. The photoluminescence spectrum of the glycocluster showed extremely strong emission at 474 nm and the absolute quantum yield was estimated to be 92% in distilled water. The emission intensity was decreased by increasing the amount of peanut agglutinin (PNA), a lactose-binding lectin, and plots of the relative fluorescence intensity revealed a decline of 95% in emission intensity. Fluorescence quenching of the glycocluster upon mixing with PNA could be easily observed by the naked eye under UV irradiation, whereas no distinct change in fluorescence properties of the glycocluster was observed when wheat germ agglutinin (WGA) was employed.     

Glycosylated tris-bipyridine ferrous complexes for probing a mechanism behind carbohydrate-carbohydrate interactions: Spatial carbohydrate packing of glycoclusters changes on additions of salts in carbohydrate- and anion-dependent manners

2,2′-Bipyridines containing two β-maltoside, β-lactoside, or β-isomaltoside appendages were prepared and successively complexed with ferrous ion to afford hexavalent glycoclusters having tris-bipyridine ferrous complex cores. Each of these metalloglycoclusters showed unique UV–vis and CD spectral changes upon addition of chloride, nitrate, and sulfate salts in carbohydrate- and anion-dependent manners. The results indicate that spatial carbohydrate packing of the metalloglycoclusters changes upon addition of these anions and that different anions stabilize different carbohydrate packings. Furthermore, the sulfates specifically enhance the rheological properties of aqueous solutions containing the metalloglycocluster containing β-lactoside appendages.     

Fluorescence quenching of triazatruxene-based glycocluster induced by peanut agglutinin lectin

A novel triazatruxene-based fluorescent glycocluster was synthesized and its selective binding interactions with PNA lectin were investigated by fluorescence spectroscopy,CD spectroscopy,and a turbidity assay.The glycocluster exhibited a strong binding affinity for PNA lectin with a Stern-Volmer quenching constant of 5.8×10⁵ mol^-1L