Structures Of Glycopolymers Research Articles

Bayesian optimization of glycopolymer structures for the interaction with cholera toxin B subunit.

The optimal structure of synthetic glycopolymers for GM1 mimetics was determined through Bayesian optimization. The interactions of glycopolymers carrying galactose and neuraminic acid units in different compositions with cholera toxin B subunit (CTB) were assessed by an enzyme-linked immunosorbent assay (ELISA). Gaussian process regression, using the ELISA results, predicted the composition of glycopolymers that would exhibit stronger interactions with CTB. Following five cycles of optimization, the glycopolymers carrying 60 mol% galactose and 25 mol% neuraminic acid demonstrated an IC50 value of 75 μM for CTB, representing the lowest value among the synthesized glycopolymers.

Cell wall galactofuranan and pyruvate-containing galactomannan in the cell walls of Clavibacter strains

The cell wall glycopolymer structures of plant-associated strains Clavibacter sp. VKM Ac-1371, Clavibacter sp. VKM Ac-1372 and Clavibacter sp. VKM Ac-1374, members of three putative new species (family Microbacteriaceae, class Actinobacteria) were studied. Each strain was found to contain two glycopolymers, neutral and acidic ones. The main chain of neutral polymer, identical in all three strains, is (1 → 6)-linked β-d-galactofuranan with every second galactofuranose residue substituted at position 2 by side disaccharide, α-d-Manp-(1 → 2)-α-d-Ribf-(1 → . The second, acidic polymer, is pyruvate-containing galactomannan with the repeating unit, →3)-α-d-Galp-(1 → 3)-α-d-[4,6-S-Pyr]-Manp-(1 → 3)-α-d-Manp-(1 → . Reducing mannopyranose residues of the acidic polysaccharides repeating unit from strains VKM Ac-1372 and VKM Ac-1374 bear O-acetyl residues additionally. The cell wall glycopolymer structures were established by chemical and NMR spectroscopic methods with using one- and two-dimensional techniques 1H,1H COSY, TOCSY, ROESY and 1H,13C HSQC, HMBC. The results obtained provide new data on diversity of the bacterial cell wall glycopolymers and may prove valuable for microbial taxonomy and insight into the molecular mechanisms of interactions between bacteria and plants and also of bacterial adaptation to survival in desert systems.

Influence of Monomer Structures for Polymeric Multivalent Ligands: Consideration of the Molecular Mobility of Glycopolymers.

Molecular mobility is important for interactions of biofunctional polymers with target molecules. Monomer structures for synthetic biofunctional polymers are usually selected based on their compatibility with polymerization systems, whereas the influence of monomer structures on the interaction with target molecules is hardly considered. In this report, we evaluate the correlation between the monomer structures of glycopolymers and their interactions with concanavalin A (ConA) with respect to the molecular mobility. Two types of glycopolymers bearing mannose are synthesized with acrylamide or acrylate monomers. Despite the similar structures, except for amide or ester bonds in the side chains, the acrylate-type glycopolymers exhibit stronger interaction with ConA both in the isothermal titration calorimetry measurement and in a hemagglutination inhibition assay. Characterization of the acrylate-type glycopolymers suggests that the higher binding constant arises from the higher molecular mobility of mannose units, which results from the rotational freedom of ester bonds in their side chains.

Novel galactofuranan and pyruvylated galactomannan in the cell wall of Clavibacter michiganensis subsp. michiganensis VKM Ac-1403T

The cell wall of Clavibacter michiganensis subsp. michiganensis VKM Ас-1403Т (family Microbacteriaceae, class Actinobacteria) contains two polysaccharides. The first one is neutral (1 → 6) linked galactofuranan in which every second galactofuranose residue in the main chain substituted at position 3 by side trisaccharide, β-D-GlcpNAc-(1 → 3)-α-L-Rhap-(1 → 2)-α-D-Fucp-(1 →. The second polymer is pyruvylated galactomannan with the repeating unit, →3)-α-D-Galp-(1 → 3)-α-D-[4,6-S-Pyr]-Manp-(1 → 3)-α-D-Manp-(1 →. The cell wall glycopolymer structures were established by chemical and NMR spectroscopic methods. The obtained results provide new data on the cell wall composition of plant pathogenic species of the genus Clavibacter and can promote understanding the molecular mechanisms involved in colonization and infection of plants.

Biodegradation Pattern of Glycopolymer Based on D-Mannose Oligomer and Hydroxypropyl Acrylate.

Glycopolymers are polymers with sugar moieties which display biodegradable and/or biocompatible character. They have emerged as an environmentally-friendly solution to classical synthetic polymers and have attracted significant research interest in the past years. Herein, we present the synthesis of a D-mannose based glycopolymer with biodegradable features. The glycopolymer was synthesized by radical copolymerization between a D-mannose oligomer bearing polymerizable double bonds and 2-hydroxypropyl acrylate, in a weight ratio of 1:2. The copolymerization kinetics was investigated by differential scanning calorimetry (DSC) and the activation energy of the process was comparatively assessed by Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa methods. The obtained glycopolymer displayed good thermal behavior, fact proven by thermogravimetrical (TG) analysis and it was submitted to biodegradation inside a bioreactor fed with water from the Bega River as the source of microbial inoculum. The glycopolymer sample degraded by approximately 60% in just 23 days. The biodegradation pattern of the glycopolymer was successfully fitted against a modified sigmoidal exponential function. The kinetic model coefficients and its accuracy were calculated using Matlab and the correlation coefficient is more than promising. The changes inside glycopolymer structure after biodegradation were studied using TG and FTIR analyses, which revealed that the sugar moiety is firstly attacked by the microbial consortia as nutrient source for proliferation.

Biodegradation studies on new glycopolymers derived from oligomeric d-mannose itaconates and 2-hydroxypropyl acrylate

We have synthesized herein new glycopolymers derived from sugar (d-mannose) oligomers with itaconic moiety and 2-hydroxypropyl acrylate in different weight ratios (1:1, 1:2, 1:3 and 1:4), in bulk, using benzoyl peroxide as initiator. These glycopolymers were characterized using FTIR spectroscopy, TG analysis, SEM, while their copolymerization process was studied from kinetics point of view using DSC. Biodegradation studies were performed in the microbiology laboratory using in situ grown cultures, provided by water taken out of Bega River that crosses Timişoara (Romania). The glycopolymer with the greatest sugar content displayed the best biodegradation pattern, losing more than 45% of its weight in just 14 days of incubation in water, at 37 °C. The thermal stability analysis was run again on the biodegraded samples and proved dramatical changes in thermal behavior profile, indicating sugar skeleton altering after a 14 days exposure to microbial environment. FTIR spectroscopy performed before and after biodegradation process revealed important changes in glycopolymer structure suggesting the sugar moiety has been the subject of microbial attack.

New glycopolymers containing both D- and L-rhamnopyranoses from Rathayibacter iranicus VKM Ac-1602T cell wall

The cell wall of Rathayibacter iranicus VKM Ac-1602T (family Microbacteriaceae, class Actinobacteria) is characterised by the absence of phosphate-containing and by the presence of two rhamnose-containing glycopolymers. The first is a branched rhamnomannan, in which 60% of mannose residues of the main chain are glycosylated by terminal mannose residues: →2)-α-D-Rhap-(1 → 3)-α-[α-D-Manp-(1 → 6)]-D-Manp-(1 → . The second is a branched teichuronic acid, in which all the rhamnose residues of the main chain are glycosylated by glucose residues:→3)-α-[α-D-Glcp-(1 → 2)]-L-Rhap-(1 → 4)-β-D-GlcpA-(1 → 2)-α-D-Manp-(1 → 3)-α-D-Galp-(1 → 3)-β-D-Glcp-(1 → . Both glycopolymers have the unique structures and described in the cell walls of Gram-positive bacteria for the first time. The obtained data allow for a more complete characterisation of the cell wall of the microorganism under investigation and can serve as a phenotypic characterisation of this bacterium. The glycopolymer structures were established using chemical and nuclear magnetic resonance (NMR) spectroscopy methods.

Single-Chain Glycopolymer Folding via Host-Guest Interactions and Its Unprecedented Effect on DC-SIGN Binding.

Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host-guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR and dynamic light scattering. The lectin binding profiles consistently provided an unprecedented effect of single chain folding as the single-chain folded structures enhanced greatly the binding ability in comparison to the unfolded linear structures.

Controlling the lectin recognition of glycopolymers via distance arrangement of sugar blocks.

The arrangement of sugars in glycopolymers contributes to their recognition. The molecular recognition of proteins was controlled by the living radical polymerization of glycopolymers. The glycopolymers were prepared by the copolymerization of propargyl methacrylate (Pr-MA) and triethyleneglycol methacrylate (TEG-MA) via living radical polymerization with a reversible addition-fragmentation glycopolymer chain transfer (RAFT) reagent and by subsequent sugar conjugation by click chemistry. The block copolymers were prepared by the polymerization of Pr-MA and TEG-MA. The molecular recognition of glycopolymers was analyzed using the fluorescence quenching of lectin and found to be dependent on the glycopolymer structures. Two-site binding of glycopolymers to concanavalin A (ConA) was attained by both the glycopolymer with a 105-mer and the tri-block glycopolymer with a 103-mer. Glycopolymers with either a 27- or 54-mer showed much weaker interaction because of one-site binding. The molecular recognition of the glycopolymer was controlled by the arrangement and size of the sugar cluster and not by the sugar density.

Design of Glycopolymers Carrying Sialyl Oligosaccharides for Controlling the Interaction with the Influenza Virus.

We designed glycopolymers carrying sialyl oligosaccharides by "post-click" chemistry and evaluated the interaction with the influenza virus. The glycopolymer structures were synthesized in a well-controlled manner by reversible addition-fragmentation chain transfer polymerization and the Huisgen reaction. Acrylamide-type monomers were copolymerized to give hydrophilicity to the polymer backbones, and the hydrophilicity enabled the successful introduction of the oligosaccharides into the polymer backbones. The glycopolymers with different sugar densities and polymer lengths were designed for the interaction with hemagglutinin on the virus surface. The synthesized glycopolymers showed the specific molecular recognition against different types of influenza viruses depending on the sugar units (6'- or 3'-sialyllactose). The sugar density and the polymer length of the glycopolymers affected the interaction with the influenza virus. Inhibitory activity of the glycopolymer against virus infection was demonstrated.

Hemicellulosic Polysaccharides Mimics: Synthesis of Tailored Bottlebrush-Like Xyloglucan Oligosaccharide Glycopolymers as Binders of Nanocrystalline Cellulose.

We report in this contribution that while low molecular weight hemicellulosic building blocks are known not to interact with cellulosic materials, their multivalent presentation on a polymeric scaffold significantly enhanced the binding interactions that are remarkably in the same range as those usually observed for lectin-carbohydrate interactions. We developed a poly(propargyl methacrylate) scaffold on which we conjugated, by "post-click" reaction, a variety of azide reducing-end functionalized xyloglucan oligosaccharides with controlled enzymatic-mediated rate of degalactosylation. Bottlebrush-like xyloglucan oligosaccharide glycopolymers (poly(XGOn)) were obtained and their self-assemblies in aqueous solution were investigated using dynamic light scattering (DLS). We demonstrated that increasing the extent of degalactosylation promoted self-association of poly(XGOn), which we attribute to the appearance of hydrophobic domains. A sharp thermoresponsiveness, which corresponds to a decrease in aggregate size with increasing temperature, was observed when the extent of degalactosylation was 30% or greater. Importantly, isothermal titration calorimetry (ITC) and polarized/depolarized DLS revealed that poly(XGOn) exhibit a significant capacity to interact with nanocrystalline cellulose (NCC) surfaces particularly for the nondegalactosylated form, emphasizing the important role of galactosyl residues in the binding mechanism and in the 3-dimensional structures of glycopolymers.

Mannose‐based graft polyesters with tunable binding affinity to concanavalin A

ABSTRACTGlycopolymers have been widely used to understand the interactions between carbohydrates and lectins, which facilitate the diagnosis and detection of disease and pathogens as well as the development of vaccines. While studies have been focused on the correlation of glycopolymer structure and their binding to lectins, graft‐type glycopolyesters are uncommon. Herein, we report the design and synthesis of mannose‐based graft polyesters by “grafting‐from” method and investigate their interactions with Concanavalin A (Con A). As confirmed by 1H NMR spectroscopy and sulfuric acid‐UV method, graft polyesters with different lengths of mannose graft were successfully synthesized. Our results from turbidimetry binding assay showed that graft polyesters with longer mannose graft exhibit higher initial binding rate (ki). Isothermal titration calorimetry measurements of these graft polyesters with Con A showed that polymers exhibit higher binding affinity (ka) with the number of side chain mannose. This study provides understanding of the interaction between Con A and mannose‐based graft polyesters, which can be employed for the development of glycopolymeric therapeutics. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3908–3917

Pyruvylated cell wall glycopolymers of Promicromonospora citrea VKM A≿-665T and Promicromonospora sp. VKM A≿-1028

The cell walls of two strains of the genus Promicromonospora (phylum Actinobacteria) were found to include non-phosphorylated anionic glycopolymers with pyruvic acid acetals of R-configuration. The cell wall of the type strain P. citrea 665T contains two glycopolymers of the sort, including the Kdn-teichulosonic acid with the repeating unit →6)-α-d-Gl≿p/→6)-α-d-Gl≿p3SO3−-(1 → 4)-α-[7,9Pyr]-Kdn-(2→, and the galactan with the repeating unit →3)-α-[4,6Pyr]-d-Galp-2OAc-(1 → . The cell wall of Promicromonospora sp.VKM Ac-1028 contains the teichuronic acid with the repeating unit →6)-α-d-Gl≿p-(1 → 4)-β-[2,3Pyr]-d-GlcpA-(1 → . The detected glycopolymer structures are reported for the first time. Presented results expand the notion on the diversity of the organic world and on the role of the structures and composition of cell wall polymers in bacterial taxonomy. The glycopolymer structures were established by using a combination of chemical methods, NMR- and IR-spectroscopy, and ESI MS.

Oligosaccharide shells as a decisive factor for moderate and strong ionic interactions of dendritic poly(ethylene imine) scaffolds under shear forces.

For better understanding and improving the non-covalent interactions of dendritic core-shell, we evaluated the interactions of hyperbranched poly(ethylene imine) (PEI) decorated with various oligosaccharide shells with water-soluble B vitamins, an estradiol derivative and pantoprazole. Depending on the different properties of the analyte molecules, dendritic core-shell glyco architectures showed (very) weak, moderate and strong interactions with the analyte molecules. Thus, ionic interactions are the strongest driving force for the formation of host-guest complexes. The core-shell glyco architecture is a necessary prerequisite for stable analyte/PEI complexes; the pure hyperbranched PEI did not show any sufficiently strong interactions with neutral, cationic or anionic analytes under the shear forces applied during ultrafiltration of pure aqueous solution without an adjusted pH. Thus, only robust non-covalent interactions between analytes and the dendritic polyamine scaffold of the glycopolymer structure survive this separation step and allow isolation of stable host-guest complexes in aqueous solution.

Preparation of amphiphilic glycopolymers with flexible long side chain and their use as stabilizer for emulsion polymerization

A glycomonomer was synthesized from poly(ethylene glycol) methacrylate (PEGMA). The terminal hydroxyl moieties were activated with ester groups and subsequently the glucosamine was incorporated forming urethane linkages. The obtained glycomonomer was copolymerized with methyl acrylate by free radical polymerization varying the initial feed composition to produce different amphiphilic glycopolymers. The glycopolymers were then characterized and compared with the homologous glycopolymers based on 2-{[(d-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate. Both series of glycopolymers were used in emulsion polymerization of methyl acrylate as stabilizers without the addition of any cosurfactant. Although high conversions were not achieved with any of the employed surfactant, the glycopolymers provide good colloidal stability, spherical, monodisperse and small latex particles in comparison with the surfactant-free emulsion polymerization. The latex particles stabilized with the glycosurfactant based on PEGMA, containing a flexible spacer between the backbone and the glucosamine, lead to smooth films whereas the short side chain surfactant from 2-hydroxyethyl methacrylate (HEMA), with higher glass transition temperature, restricts the coalescence of particles and, therefore, the film formation. Moreover, the surface bioactivity of these polymer coatings was examined by analyzing their specific interaction with the lectin, Concanavalin A, Canavalia ensiformis. The specific and successful binding to the Concanavalin A was demonstrated by fluorescence microscopy for both series being more intense with increasing amount of glycounits in the glycopolymer stabilizers. Interestingly, the incorporation of a flexible spacer in the glycopolymer structures enhances the binding activity.

Structures of cell-wall phosphate-containing glycopolymers of Bifidobacterium longum BIM B-476-D

Glycopolymers with oligosaccharyl phosphate repeats of two types and ribitol and glycerol teichoic acids were isolated from cell wall of Bifidobacterium longum BIM B-476-D by stepwise extraction with 10% CCl3CO2H. The following structures of the glycopolymers were established by sugar analysis, selective cleavage with aq 2% HOAc, dephosphorylation with 48% HF, 2D NMR spectroscopy, and high-resolution ESI MS: [Display omitted] The ribitol teichoic acid also contains minor d-alanine, whose position was not determined.

Glycopolymer Brushes for the Affinity Adsorption of RCA120: Effects of Thickness, Grafting Density, and Epitope Density

The interactions between glycopolymer brushes and lectin are very important for the development of affinity membrane chromatography in protein separation. Here, we report the combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and surface plasmon resonance (SPR) to investigate the relationship between the structure of glycopolymer brushes and the affinity adsorption of lectin. The glycopolymer brushes were fabricated from self-assembly of 11-mercapto-1-undecanol (MUD)/1-undecanethiol (UDT) mixture, immobilization of ATRP initiators, and then SI-ATRP of 2-lactobionamidoethyl methacrylate (LAMA). Brush thickness and grafting density were adjusted by controlling polymerization time and thiol ratio in MUD/UDT mixture, respectively. Sugar epitope density was also controlled through copolymerization of 2-hydroxylethyl methacrylate (HEMA) with LAMA. Ricinus communis agglutinin (RCA(120)), one kind of lectin that can bind galactose specifically, was chosen to study the effects of brush architectures on lectin adsorption. SPR results indicate not only the thickness but also the grafting density and the epitope density of glycopolymer brushes can achieve the best performance of sugar cluster effect in affinity adsorption of lectin. In addition, the mass transport effect is crucial in the adsorption process. We propose that it is important to keep the balance between the sugar cluster effect and the mass transport effect in the preparation of high-performance affinity membrane chromatography.

Design and synthesis of well-defined glycopolymers for the control of biological functionalities

Glycopolymers with pendant saccharides are biofunctional polymers that interact with saccharide recognition proteins. The glycopolymers show the strong molecular recognition ability owing to the multivalency. These polymers were prepared by the polymerization with sugar derivatives or by the saccharide addition to the polymer backbone. The glycopolymers can be applied for cell cultivation, drug delivery, and biosensing. The living radical polymerization provided the precise structure of glycopolymer, which was useful for analysis of the protein–saccharide interactions. The living radical polymerization also provided the hybrid biomaterials that can be used for biosensing and biomaterials.

Neoglycopolymers Based on 4‐Vinyl‐1,2,3‐Triazole Monomers Prepared by Click Chemistry

The synthesis of a new glycomonomer based on mannose, prepared via CuAAC, is reported. The resulting 1,2,3-triazole linkage between mannose and the polymer backbone ensures the formation of highly stable glycopolymers, which will not undergo hydrolysis. The monomer 2'-(4-vinyl-[1,2,3]-triazol-1-yl)ethyl-O-alpha-D-mannopyranoside was polymerized in the presence of a RAFT agent - 3-benzylsulfanylthiocarbonylsulfanyl propionic acid - to yield well-defined polymers with molecular weights up to 51,500 g mol(-1) and a PDI of 1.16. The resulting polymer was employed as a macroRAFT agent in the polymerization of NIPAAm in order to generate thermo-responsive block copolymers, which undergo reversible micelle formation at elevated temperatures. The rapid interaction between the polymers prepared and ConA confirms the high affinity of these structures to proteins. While the linear glycopolymers already undergo a fast complexation with ConA, the reported rates have found to be exceeded by the micellar glycopolymer structure presented in the current contribution.