Supramolecular one-pot approach to fluorescent glycodendrimers

Homogeneous, fluorescent, sugar-functionalized metallic dendrimers that contain varying numbers and types of monosaccharides have been prepared using a self-assembly process and have been shown to be highly efficient lectin sensors in turbidity assays.     

Glycomimetics and glycodendrimers as high affinity microbial anti-adhesins

Adhesion to epithelial surface is often the first step in bacterial and viral infection. In this process, the microbes use a variety of proteins for interaction with host carbohydrates presented as glycoconjugates on cell surfaces. Crystal structures of adhesin and lectin binding sites in complexes with oligosaccharide open the route for design and synthesis of glycomimetics, glycodendrimers, and glycopolymers that are able to block infection at an early stage.     

Sugars within a hydrophobic scaffold: glycodendrimers from polyphenylenes

A new glycodendrimer type has been introduced that is designed on the basis of shape-persistent polyphenylene dendrimers. The sugar installation occurs not only on the dendrimer surface but also within the hydrophobic internal scaffold. The synthesis has been accomplished via both convergent and divergent routes by employing the Schmidt glycosylation and the Diels-Alder reaction. This new glycodendrimer has been found to exhibit water-solubility, while conserving hydrophobicity of the interior environment despite the incorporation of sugars.     

First phosphorous d-xylose-derived glycodendrimers

Phosphorous glycodendrimers have been prepared in quantitative yields by grafting xylose-derived moieties on phosphorous dendrimers involving hydrazone units. These dendrimers could be hydrophobic or amphiphilic, respectively, with acetylated or unprotected sugar moieties.     

Syntheses of glycodendrimers having scyllo-inositol as the scaffold

Synthetic glycoconjugated dendrimers have emerged as important functional glycomimetics for studying multivalency effects in the cell-cell communications. We report herein, a synthetic route to functionalized glycodendrimers with scyllo-inositol as the scaffold, which have a directed geometry; one side of the dendrimers is designed for ready attachment to the AFM probe/solid matrix, and the other to have a varying number of a sugar.     

Potentiation of fibroblast growth factor activity by synthetic heparin oligosaccharide glycodendrimers

Heparin is a highly sulfated polysaccharide that regulates a variety of cellular processes by interaction with a host of proteins. We report the preparation of synthetic heparin oligosaccharide glycodendrimers and their use as heparin mimetics to regulate heparin-protein interactions. The multivalent display of sugar epitopes mimics the naturally occurring glycans found on cell surfaces and enhances their binding capacity. Binding of the heparin dendrimers to basic fibroblast growth factor (FGF-2) was analyzed using heparin microarray experiments and surface plasmon resonance measurements on gold chips. Heparin-coated dendrimers bind FGF-2 significantly more effectively than monovalent heparin oligosaccharides. Dendrimer 1, which displays multiple copies of the sulfated hexasaccharide (GlcNSO(3)[6-OSO(3)]-IdoA[2-OSO(3)])3, was employed to promote FGF-2-mediated mitogen-activated kinase activation, demonstrating the utility of glycodendrimers to modulate heparin-protein interactions.     

Water-soluble glycodendrimers: synthesis and stabilization of catalytically active Pd and Pt nanoparticles

A new water-soluble glycodendrimer containing 9 terminal modified xylose branches was prepared from nona-azide terminated dendrimer by ‘click’ chemistry. The glycodendrimer was analyzed by ¹H, ¹³C NMR and mass spectroscopy and used to stabilize palladium (PdNPs) and platine (PtNPs) nanoparticles. These DSN are stable in water and were characterized by TEM. The platinum NPs showed a remarkable catalytically activity for olefin hydrogenation in water at room temperature.     

Hexaphenylbenzene as a rigid template for the straightforward syntheses of "star-shaped" glycodendrimers

Original glycodendrimers emanating from propargylated hexaphenylbenzene cores and containing up to 54 peripheral sugar ligands have been synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloadditions using both convergent and divergent approaches.     

First synthesis of "Majoral-Type" glycodendrimers bearing covalently bound alpha-D-mannopyranoside residues onto a hexachlocyclotriphosphazene core

A short and efficient strategy for the first synthesis of "Majoral-Type" multivalent glycodendrimers bearing covalently bound alpha-D-mannopyranosides onto a cyclotriphosphazene scaffold assembled using single-step Sonogashira and click chemistry is reported. New glycoclusters with valencies ranging from 6 to 18 and different epitope spatial arrangements were obtained. Cross-linking abilities of this series of glycodendrimers were evaluated with the model lectin from Canavalia ensiformis (Concanavalin A). The decameric mannoside 23, built around 19, was shown to be much faster in cross-linking the tetravalent lectin Concanavalin A than the positive control, which is the polysaccharide mannan from yeast. The new glycoconjugates reported may be promising tools as probes or effectors of biological processes involving multivalent carbohydrate-binding proteins.     

Synthesis and in vitro anti-arthritic,anti-inflammatory studies on hypervalent pyranoside glycodendrimers with triazole bridging point

Synthesis of novel glycodendrimer scaffolds containing hypervalent sugar pyranosides and triazole bridging points is described. Dendrimers with a greater number of bridging triazole units and α-d-glycopyranosyl surface groups exhibit better anti-arthritic and anti-inflammatory activity than dendrimers with less number of triazole and α-d-glycopyranosyl units.     

Synthesis of N,N'-bis(acrylamido)acetic acid-based T-antigen glycodendrimers and their mouse monoclonal IgG antibody binding properties.

Novel glycodendrimers based on N,N'-bis(acrylamido)acetic acid core with valencies between two and six were synthesized. The breast cancer-associated T-antigen carbohydrate marker, (beta-Gal-(1-3)-alpha-GalNAc-OR), was then conjugated by (i) 1,4-conjugate addition of thiolated T-antigen to the N-acrylamido dendritic cores and by (ii) amide bond formation between an acid derivative of the T-antigen and the polyamino dendrimers. The protein-binding ability of these new glycodendrimers was fully demonstrated by turbidimetric analysis and by enzyme-linked immunosorbent assay (ELISA) using peanut lectin from Arachis hypogaea and a mouse monoclonal antibody (MAb) FAA-J11 (IgG3). When tested as inhibitors of binding between MAb and a polymeric form of the T-antigen (T-antigen-co-polyacrylamide) used as a coating antigen, di- (17), tetra- (20), hexa- (21), and tetravalent (22) dendrimers showed IC(50) values of 174, 19, 48, and 18 nM, respectively. Two tetramers showed 120- to approximately 128-fold increased inhibitory properties over the monovalent antigen 6 used as a standard (IC(50) 2.3 mM). Heterobifunctional glycodendrimer bearing a biotin probe was also prepared for cancer cell labeling.     

Thiol‐ene and thiol‐yne‐based synthesis of glycodendrimers as nanomolar inhibitors of wheat germ agglutinin

Alkene and alkyne functional polyester‐based dendrimers of generation 1 to 4 have been prepared and reacted under free‐radical conditions with 2‐acetamido‐2‐deoxy‐1‐thio‐β‐D ‐glucose (GlcNAc‐SH). As the alkene‐dendrimers underwent the addition of one thiyl radical per ene group whereas each yne group of alkyne‐dendrimers was saturated by two thiyl radicals, a collection of glycodendrimers with glycan density ranging from six to ninety‐six GlcNAc per dendrimer was obtained. The recognition properties of the prepared glycodendrimers toward the wheat germ agglutinin (WGA) were evaluated by enzyme‐linked lectin assay (ELLA). The eight glycodendrimers were excellent ligands showing IC₅₀ values in the nanomolar range and relative potencies per sugar unit up to 2.27 e⁶ when compared to monosaccharidic GlcNAc used as monovalent reference. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2422–2433     

Non-covalent polyvalent ligands by self-assembly of small glycodendrimers: a novel concept for the inhibition of polyvalent carbohydrate-protein interactions in vitro and in vivo

Polyvalent carbohydrate-protein interactions occur frequently in biology, particularly in recognition events on cellular membranes. Collectively, they can be much stronger than corresponding monovalent interactions, rendering it difficult to control them with individual small molecules. Artificial macromolecules have been used as polyvalent ligands to inhibit polyvalent processes; however, both reproducible synthesis and appropriate characterization of such complex entities is demanding. Herein, we present an alternative concept avoiding conventional macromolecules. Small glycodendrimers which fulfill single molecule entity criteria self-assemble to form non-covalent nanoparticles. These particles-not the individual molecules-function as polyvalent ligands, efficiently inhibiting polyvalent processes both in vitro and in vivo. The synthesis and characterization of these glycodendrimers is described in detail. Furthermore, we report on the characterization of the non-covalent nanoparticles formed and on their biological evaluation.     

Large Cyclodextrins

The existence of large cyclodextrins, cyclic -D-(1 4) glucans with a degree of polymerisation higher than eight, has been proven during the past decade. A number of 4- -glucanotransferases have been shown to be able to produce large cyclodextrins consisting of up to several hundred glycosyl units, from both amylose and amylopectin. Large cyclodextrins with degree of polymerisation up to 31 have been isolated to purity by use of elaborate purification schemes, enabling studies of their structural and complex forming properties. The solid state structures of the large cyclodextrins with a degree of polymerisation 10, 14 and 26, respectively, have revealed interesting new structural features of this family of molecules. This review summarises the studies of the large cyclodextrins, a varied and highly interesting group of molecules.     

Very Large Cyclic Compounds

Very large ring systems, containing more than 50 ring members, are becoming increasingly important in different topics in natural sciences. These so-called gigantocycles differ from smaller macrocycles in physical properties, special structural features and chemical behaviour. This article is meant to be the first summary of such ring systems and a synopsis of the most remarkable examples with their fascinating nano-scaled structures and ingenious synthesis. To restrict the scope of the article, only isolated and completely characterized, monodisperse compounds are presented. Furthermore, attention is mainly directed at organic gigantocycles. Some ultracycles with more than 100 ring members, mainly occurring in polymer chemistry and nature, will also be described.     

Activation Analysis of Large Samples

The usual mass of samples for activation analysis is in the range of several milligrams to several hundred milligrams. An improvement of the detection limit by three orders of magnitude is attainable by use of a larger sample size. Limitations of the method due to thermal effects, neutron self-shielding and gamma-ray attenuation during activation and measuring of large organic samples are discussed.