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The capability of a polymer to depolymerize, regenerating its original monomer for further polymerization, is very attractive in terms of sustainability. Recently discovered sugar poly(orthoesters) are an important class of glycopolymer. The high sensitivity of the backbone orthoester linkage toward acidolysis provides a valuable model to study the depolymerization. Herein, a sugar poly(orthoester) is shown to be completely depolymerized under acidic conditions. Interestingly, instead of the original monomer, the depolymerization gave a stable cyclic product (1,6-anhydro glucopyranose) in most cases, which was kinetically and thermodynamically favored. However, this pathway could be inhibited by chemically deactivating a key intermediate and thus favoring the formation of the original monomer. Efficient repolymerizaton of the regenerated monomer is also demonstrated.

Near infrared fluorescent galactose targeted glycopolymer containing m-carborane has been synthesized through ring open and atom transfer radical polymerization, followed by post-functionalization ...

Glycopolymers 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

The weak binding between carbohydrates and proteins is a major constraint toward the development of carbohydrate-based therapeutics. To address this, here we report the synthesis of glycopolymer (GP)-grafted silica nanoparticles (SiNP) by using reversible addition–fragmentation chain transfer (RAFT) polymerization through the grafting-from approach using a multistep process. GP chains of various lengths with controlled molecular weight and narrow polydispersities were grown on the RAFT agent anchored SiNP surface using mannosyloxyethyl methacrylate (MEMA) as a glycomonomer. Spectroscopic (FT-IR, NMR) and thermogravimetric studies confirmed the grafting of poly(MEMA) chains on the SiNP surface and also showed that the dry DMF is a better solvent as compared to water/ethanol mixture for carrying out the MEMA polymerization on SiNP surface. The mean diameter of the dry GP-grafted SiNPs (GP-g-SiNPs) obtained from microscopic studies was in the range 50–60 nm, whereas the hydrodynamic diameter as obtained usin...

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.

The fabrication of microarrays consisting of well-defined glycopolymers is described. This was achieved by postfunctionalization of an immobilized poly(allyl glycidyl ether) using unprotected thiol-modified carbohydrates through thiol–ene conjugation chemistry. This enabled the fabrication of glycopolymer microarrays in which the density and composition of the carbohydrate moieties varied along each of the polymer chains displayed across the array. These glycopolymer microarrays were applied in the evaluation of multivalent ligand–protein interactions with the determination of surface dissociation constants (KD) with concanavalin A and Ricinus communis agglutinin I for surface immobilized mannose-, glucose-, and galactose-containing glycopolymers and validated in solution with ITC.

Electrospun biodegradable membranes have attracted great attention for a range of tissue engineering applications. Among them, poly(e-caprolactone) (PCL) is one of the most widely used polymers, owing to its well-controlled biocompatibility and biodegradability. However, PCL also has a number of limitations, such as its hydrophobic nature and the lack of functional groups on its side chain, limiting its ability to interact with cells. Herein, we have designed and prepared a series of well-defined A2B-miktoarm copolymers with PCL and glycopolymer segments to address these limitations. Moreover, copolymers were electrospun to make membranes, which were studied in vitro to investigate cell affinity, toxicity, activity, and adhesion with these materials. The results indicate that incorporating glucose moieties into miktoarm polymers has improved the biocompatibility of the PCL while increasing the cellular interaction with the membrane material.

Biomaterial surfaces can possess chemical, topographical, or electrostatic heterogeneity, which can profoundly influence their performance. By developing experimental models that reliably simulate this nanoscale heterogeneity, we can predict how heterogeneous surfaces are transformed by their interactions with the dynamic physiological environment. In this work, we present a model surface where well-defined glycopolymer brushes are interspersed with positively charged binding sites, giving rise to an interface presenting a mixture of repulsive and adhesive cues to an approaching virus particle. We show that the density of the affinity sites relative to the glycopolymer brushes can be tuned precisely by modifying the chemical vapor deposition (CVD) copolymerization conditions. Further, we examined the effects of binding site density and glycopolymer brush architecture on the adsorption kinetics of virus-like nanoparticles through a novel approach employing time-resolved ζ-potential measurements. Most materials have charge-bearing, dynamic surfaces that are sensitive to electrostatic effects. Hence, adsorption-triggered changes in ζ-potential measurements can be captured in real time to monitor interfacial events. Real-time ζ-potential measurements present an interesting platform to probe the structure and function of chemically and electrostatically heterogeneous polymer interfaces. To validate this electrokinetic method, we examined the effect of neutravidin concentration on its rate of binding to biotinylated surfaces using ζ-potential and compared our results with QCM studies. By applying electrokinetic methods to examine the roles of glycopolymer brush architecture and surface charge of these tunable glycopolymer coatings, we can enhance our understanding of the interactions of viruses with heterogeneous biomaterial interfaces.

Aminophenylboronic acid (ABA) modified bovine serum albumin (BSA) was prepared as neolectin and its interactions with oligosaccharides and glycopolymer were studied by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). The conjugation between the primary amine group of the ABA molecule and lysine residues on BSA was performed with an adipate-based strategy to afford the synthetic neoprotein. The number of ABA molecules loaded to BSA surface was determined by matrix-assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry. In the BSA-ABA and sugar interaction study, no signal was observed for both the SPR and ITC sensor platform using monosaccharides as the analyte, indicating a weak binding affnity, while the galactose modified polymer showed an enhanced response. The binding affinities of the galactosyl-polymer to BSA-ABA from SPR and ITC data were in the micromolar range.

Two pH-sensitive Glycopolymers with the same components but with different construction tailored biotin functionalities were developed for controlled release of bortezomib (BTZ).The initiator brominate biotin and glyco-monomer were synthesized precedently to produce the block-and random-biotinylated poly (2-Gluconamidoethyl methacrylate)-poly (2-Diethylaminoethyl methacrylate) (block/random Biotin-PGAMA-PDEA) via atom transfer radical polymerization (ATRP). The construction and composition of compounds and polymers were characterized by 1H NMR Spectroscopy. The block copolymer self-assembled into micelle according to the pH-response ability of the copolymer while the random one did not under certain conditions.

Shaofeng Lou,1 Xiuyuan Zhang,2 Mingming Zhang,2 Shenglu Ji,1 Weiwei Wang,2 Ju Zhang,1 Chen Li,2 Deling Kong1,2 1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People’s Republic of China Abstract: A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy. Keywords: glycopolymer, multi-responsive nanogel, hepatoma targeting, drug delivery, arm-first ATRP

Shaofeng Lou,1 Xiuyuan Zhang,2 Mingming Zhang,2 Shenglu Ji,1 Weiwei Wang,2 Ju Zhang,1 Chen Li,2 Deling Kong1,2 1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People’s Republic of China Abstract: A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy. Keywords: glycopolymer, multi-responsive nanogel, hepatoma targeting, drug delivery, arm-first ATRP

Regardless of the route of administration, some or all of a therapeutic agent will appear in the blood stream, where it can act on blood cells and other components of the plasma. Recently we have shown that poly(ethylene imines) (PEIs) which interact with plasma proteins are taken up into erythrocyte membranes. These observations led us to investigate the interactions between maltose functionalized hyperbranched PEIs (PEI-Mal) and plasma proteins. Two model proteins were chosen − human serum albumin (HSA) (albumins constitute ∼60% of all plasma proteins), and lysozyme. HSA is a negatively charged 66kDa protein at neutral pH, whereas lysozyme is a positively charged 14kDa protein. Fluorescence quenching and changes in the conformation of the amino acid tryptophan, diameter and zeta potential of proteins were investigated to evaluate the interaction of PEI-Mal with proteins. PEI-Mal interacts with both types of proteins. The strength of dendritic glycopolymer interactions was generally weak, especially with lysozyme. Greater changes were found with HSA, mainly triggered by hydrogen bonds and the electrostatic interaction properties of dendritic glycopolymers. Moreover, the structure and the size of PEI-Mal macromolecules affected these interactions; larger macromolecules with more sugar groups (95% maltose units) interacted more strongly with proteins than smaller ones with lower sugar modification (33% maltose units). Due to (i) the proven overall low toxicity of sugar-modified PEIs and, (ii) their ability to interact preferentially through hydrogen bonds with proteins of human plasma or possibly with other interesting protein targets, PEI-Mal is a good candidate for creating therapeutic nanoparticles in the fast developing field of nanomedicine.

We report a straightforward synthesis of N-glycan polymers from free glycans via glycosylamine intermediates followed by acrylation and polymerization via cyanoxyl-mediated free radical polymerization (CMFRP) in one-pot fashion. No protection and deprotection were used in either glycomonomer or glycopolymer synthesis. A typical synthetic procedure for N-glycan polymers from free monosaccharide and disaccharide, Glc, Gal, Man, GlcNAc, and Lac, was demonstrated. In addition, enzymatic sialylation of the Lac-containing N-glycan polymers and their anti-influenza virus hemagglutination activities were investigated.

Photodynamic therapy (PDT) has become a promising treatment approach against cancer due to low side effects and high therapeutic efficacy. However, the limitations of photosensitizers such as poor water solubility and lack of targeting ability hindered the clinical application of PDT. Here, we synthesized a phosphorescent conjugated polymer brush (PPF-Ir-g-(POEGMA-b-PGal)) in which a small photosensitizer iridium(III) complex was covalently attached to the conjugated backbone. A further hydrophilic polymer (POEGMA) and glycopolymer polygalactose (PGal), which has a specific binding ability with Hep G2 tumors, were grafted from the conjugated backbone via atom transfer radical polymerization (ATRP) and click reaction. The brush structure rendered PPF-Ir-g-(POEGMA-b-PGal) exhibited excellent water solubility. Meanwhile, PPF-Ir-g-(POEGMA-b-PGal) showed efficient properties of producing singlet oxygen. The photodynamic effect of the PPF-Ir-g-(POEGMA-b-PGal) photosensitizer was evaluated in Hep G2 cells via the MTT assay and flow cytometry and the results indicated that this photosensitizer can efficiently cause the death of cancer cells. Additionally, an antitumor study of PPF-Ir-g-(POEGMA-b-PGal) was conducted in vivo with Hep G2 tumor bearing nude mice, and the results show that the xenograft tumors were significantly inhibited. In summary, PPF-Ir-g-(POEGMA-b-PGal) exhibited fine water solubility and high PDT efficiency both in vitro and in vivo. Our study may further encourage the applications of conjugated polymer brush based photosensitizers for PDT in tumor treatment.

A series of four-arm star copolymers, incorporating glycopolymer and antimicrobial polypeptide domains, was developed in the design of forthcoming anti-infective agents. Mannose, glucose, and galactose-based glycopolymers with a variety of well-defined chain lengths were prepared via atom transfer radical polymerization, whereas linear α-polylysine was prepared via ring-opening polymerization of N-carboxyanhydride monomers. Copper-catalyzed azide–alkyne cycloaddition was employed for ‘click’ conjugation of the glycopolymer arms and the polypeptide chains. The glycopolymer–polypeptide conjugates were non-hemolytic and exhibited higher cytocompatibility than the linear α-polylysine. The conjugates with shorter chains of mannose-based glycopolymer arms showed an enhanced bactericidal efficacy against Gram-negative and Gram-positive bacteria, with a therapeutic selectivity half of that of the linear α-polylysine. The pendant mannose moieties of the conjugates increased microbial targeting due to their specific affinity for bacterial surfaces, and binding competition with free mannopyranoside was demonstrated. Therefore, the molecular combination of glycopolymers and polypeptides without loss of their respective activities provides an interesting concept in the design of antimicrobial agents to combat infectious disease.

Here we report a simple and one-pot method for the synthesis of glycopolymer based colloidal particles with tunable core–shell morphology using reversible addition fragmentation chain transfer (RAFT) polymerization. A hydrophilic carbohydrate functionalized monomer (called glycomonomer) namely allyl-α-D-glucopyranoside (α-Glu) was polymerized with the RAFT agent to yield a macro-sugar chain, which acts as a macro-RAFT agent, and then this chain was further extended by copolymerizing the hydrophobic styrene monomer. The resulting polymer chains consist of polystyrene (PS) as a hydrophobic chain and glycopolymer (GP) as a hydrophilic chain. Several microscopic techniques which include FE-SEM, TEM, AFM and confocal Raman imaging proved the formation of core–shell colloidal particle morphology of the synthesized PS–GP in which PS was found in the core of the particle and the shell was made up of GP. The tunability in the particle size and in the core (PS)–shell (GP) dimension was achieved by altering the macro-sugar chain length and hydrophilic monomer (sugar) concentration in the polymerization feed. The formation of more number of macro-sugar chains with the increasing sugar content in the feed led to the production of a large number of smaller sized micelles in the polymerization medium which yielded smaller size particles. The colloidal stability and the molecular weight of the resulting PS–GP core–shell nanoparticles were found to be dependent upon both macro-RAFT and sugar content in the reaction feed.

A glycopolymer bearing α2,3-linked sialyltrisaccharides was synthesized by living radical polymerization using a glycomonomer prepared by a protecting-group-free process, direct azidation of the free sialyllactose, and subsequent azide-alkyne cycloaddition. The prepared glycopolymer with pendant 3´-sialyllactose moieties strongly interacted with both avian and human influenza viruses analyzed by the hemagglutination inhibition assay and the quartz crystal microbalance method.

In this paper, novel star glycopolymers were synthesized via Cu(0)-mediated radical polymerisation at ambient temperature. The reaction was fast with little star–star coupling. Moreover, star glycopolymers can be obtained without removing oxygen from the polymerisation mixture. The effects of solvent and the ratio of initiator/catalyst/ligand on polymerisation were investigated, and the optimal conditions for the synthesis of star glycopolymer were determined. In addition, the binding ability between synthesised glycopolymers and concanavalin A (ConA) was studied using a turbidity test and quartz crystal microbalance-dissipation (QCM-D). Compared with linear glycopolymers, star glycopolymers showed higher binding ability to specific lectins and the strongest binding was obtained when the molecular weight was medium.

Improving the delivery of nucleic acids to diverse tissue types in culture is important for translating genome editing for regenerative cell therapies. Herein, we examine the effect of transfection media additives, such as the sulfated glycosaminoglycan heparin, in dramatically increasing pDNA delivery efficiency and transgene expression in a wide variety of cell types. Polyplexes formed by combining pDNA and Tr4, a cationic glycopolymer containing repeated trehalose and pentaethylenetetramine groups, were treated with low concentrations of heparin prior to in vitro transfection with plasmid DNA. Polyplex formulations were found to be stable and form ternary complexes upon heparin addition according to dynamic light scattering and ethidium bromide dye exclusion assays. Heparin-coated polyplexes offer significant increases (approximately 4-fold) in GFP expression compared to polyplexes prepared with Tr4 only in primary fibroblasts, U87, and HepG2 cells. Heparin was also shown to increase GFP expression in a linear, dose-dependent manner. The heparin-treated Tr4 polyplexes exhibited more than 50% higher cellular internalization with HepG2 cells while showing minimal increases with U87 and primary fibroblasts. Pharmacological inhibition was used to further understand the endocytic pathways taken during transfection in the presence and absence of heparin. It was found that heparin-treated polyplexes are endocytosed primarily through macropinocytosis and clathrin-mediated pathways, while Tr4 polyplexes without heparin appear to be internalized primarily via caveolae. Heparin appears to also modify the nuclear localization behavior of Tr4 polyplexes, which likely contributes to increased efficiency and transgene expression.

International audience; The understanding of glycopolymer-based nanostructures formation and their lectin binding properties are of great interest to the development of drug delivery systems and other biological applications. Herein, glycosylated polypeptides were synthesized from a clickable poly(L-lysine)-b-poly(benzyl-L-glutamate) copolypeptide, obtained by a sequential ring opening polymerization. The clickable poly(L-lysine) chain was completely functionalized by introducing galactose and lactose moieties on the copolypeptide's hydrophilic block, aiming specific lectin recognition. Spheres, pearl-necklace and worm-like structures prepared from poly(L-lysine)-b-poly(benzyl-L-glutamate) copolypeptides were obtained after nanoprecipitation, depending on the hydrophilic block functionalization and the hydrophobic block length. Specific interaction between the sugars on the micelles' surface with RCA120 lectin was observed with the PBLG40-based nano-structures. However, unexpected and unspecific interactions were observed with some nanostructures, showing the importance of the chemical functionalization and nanostructure stabilization. Such a synthetic approach can be used to develop any other amphiphilic and biofunctional polypeptide-based copolymers and nanoparticles.

The macroporous monolithic stationary phase was elaborated for the efficient solid-phase extraction of cholesterol from aqueous media. The advantages of the developed monolithic materials as compared with the bead-based columns of the same functionality were demonstrated.

Corresponding authors :Douwe van Sinderen (d.vansinderen@ucc.ie) Marie-Pierre Chapot-Chartier (marie-pierre.chapot-chartier@inra.fr); International audience; In $Lactococcus\ lactis$, cell-wall polysaccharides (CWPSs) act as receptors for many bacteriophages, and their structural diversity among strains explains, at least partially, the narrow host range of these viral predators. Previous studies have reported that lactococcal CWPS consists of two distinct components, a variable chain exposed at the bacterial surface, named polysaccharide pellicle (PSP), and a more conserved rhamnan chain anchored to, and embedded inside, peptidoglycan. These two chains appear to be covalently linked to form a large heteropolysaccharide. The molecular machinery for biosynthesis of both components is encoded by a large gene cluster, named $cwps$. In this study, using a CRISPR/Cas-based method, we performed a mutational analysis of the $cwps$ genes. MALDI-TOF MS-based structural analysis of the mutant CWPS combined with sequence homology, transmission EM, and phage sensitivity analyses enabled us to infer a role for each protein encoded by the $cwps$ cluster. We propose a comprehensive CWPS biosynthesis scheme in which the rhamnan and PSP chains are independently synthesized from two distinct lipid-sugar precursors and are joined at the extracellular side of the cytoplasmic membrane by a mechanism involving a membrane-embedded glycosyltransferase with a GT-C fold. The proposed scheme encompasses a system that allows extracytoplasmic modification of rhamnan by complex substituting oligo-/polysaccharides. It accounts for the extensive diversity of CWPS structures observed among lactococci and may also have relevance to the biosynthesis of complex rhamnose-containing CWPSs in other Gram-positive bacteria.

Carbohydrates are valuable and safe sources for the synthesis of biopolymers. Today, synthetic polymers having saccharides as pedant groups are one of the great interests in biochemistry and the medicinal field. In this work, with the aim of preparing the new glyco-copolymer, firstly isopropylidene derivative of α-D-glucofuranose was synthesized from the reaction of acetone with the glucose in the presence of sulphuric acid as catalyst. Then the obtained compound separately reacted with acryloyl chloride and ρ-(chloromethyl)styrene monomers to produce related vinylic type glycomonomers. The synthesized glycomonomers were purified using column chromatography. Characterization of the synthesized vinylic glycomonomers was carried out using elemental analysis, fourier transform infrared (FT-IR), Carbon-13 nuclear magnetic resonance (13C NMR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. In the next step, the obtained glycomonomers were copolymerized in 1:1 ratio via a fast and easy free radical polymerization technique. The obtained copolymer showed good solubility in various solvents such as tetrahydrofuran, chloroform, ethyl acetate, and some of the other organic solvents. Finally, water-soluble glyco-copolymer was obtained via partial hydrolysis. The structure of the isolated copolymers determined using the 1H NMR, gel permeation chromatography (GPC), and FT-IR spectroscopy.

Glycopolymers are an important class of biomaterials which include carbohydrate moieties in their polymer structure. In addition to biological research on the interactions of glycopolymers with lectin-carbonate, glycopolymers have recently been used as a new synthetic biomaterial for direct therapeutic methods, medical adhesives, and biosensors. Thus, a comprehensive understanding of new advances in glycopolymer research is essential for the next level of biomaterial studies. This review article highlights commonly used glycopolymer synthesis methods and biomedical applications thereof. Glycopolymers can be synthesized by modern polymerization methods that can control the molecular weight, molecular weight distribution, chemical functionality, and polymer architecture. The polymerizations include free radical polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain-transfer polymerization, and nitroxide-mediated polymerization. Because the carbohydrate-lectin interactions with glycopolymers are involved in many biological processes, carbohydrates containing glycopolymers are used in (1) fundamental studies to understand the specificity and strength of biological binding, (2) controllable interactions to prevent microorganism adhesion to human cells, (3) large scale bulk adhesives for medical applications, (4) biocompatible therapeutic nanoparticles, (5) direct drug delivery vehicles, and (6) precise quantitative measurement of biosensor materials that can detect physiological signals.

Biodegradation of plastic materials is an issue of growing concern due to its tremendous environmental impact. This study presents the development of a bioreactor for aerobic biodegradation of a glycopolymer derived from D-mannose and hydroxyl-propyl methacrylate (HPMA). The bioreactor is provided with aeration system, thermoset unit and stirring system. The glycopolymer samples were degraded inside the bioreactor fed with water from Bega River, under aerobic conditions (air flow 2 l/min) at 37±0.5°C for 23 days. The samples derived from natural raw material displayed good biodegradation pattern losing more than 90% their weight, in just 23 days. FTIR and TG analyses run before and after degradation showed that the microorganisms tended to use the sugar moiety as carbon source in first instance, then they turn to synthetic carbon. The kinetic study based on the mathematical Logistic growth model proved adequate for the modeling of the weight loss vs. time. The bioreactor proved as an efficient tool for plastic material biodegradation under aerobic conditions.

Plant glycoproteins, especially allergenic glycoproteins such as pollen allergens, often carry antigenic N-glycans with α1-3 fucose and/or β1-2 xylose residue(s) on the trimannosyl core structure. We previously reported that one of such antigenic free-form N-glycans, Man3Xyl1Fuc1GlcNAc2 (M3FX) suppressed IL-4 production from Th2 cells of pollinosis patients. For the molecular-level analysis of this immunoactivity, an effective and convenient procedure for large scale preparation of the immunoactive free-form N-glycan and a synthesis of glycopolymers bearing multivalent M3FX has been required. During the preparation of prebiotic oligosaccharides from several edible beans, we found that the free-form M3FX accumulates in relatively large amounts in white kidney beans. In this report, we describe a new procedure for preparation of M3FX from white kidney bean powders by a combination of ion-exchange method, gel-filtration, and hydrophilic partitioning. The high-purity of M3FX prepared by this procedure was confirmed by MS-analysis and 1H-NMR, suggesting that the free-form M3FX can be used for the synthesis of neoglycopolymer. Using this new procedure, the immunoactive oligosaccharide can be prepared without the chemical method such as hydrazinolysis and other purification steps required to exclude other type of N-glycans.

The synthesis of brush glycopolymers mimicking the architecture of proteoglycans is achieved by grafting sequence-defined glycooligomers derived from solid-phase polymer synthesis onto a poly(active ester) scaffold. This approach gives access to a first library of brush glycopolymers with controlled variations in the degree of branching and number of carbohydrate ligands per branch. When studying lectin binding of linear and brush glycopolymers to lectins Concanavalin A (ConA), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and mannose-binding lectin (MBL), different preferences are observed with MBL showing higher binding to linear glycopolymer and ConA and DC-SIGN favoring brush glycopolymers. This finding suggests that the architecture of polymeric glycan mimetics affects binding to lectins not only in terms of creating higher avidity but potentially also selectivity ligands.

Glycopolymers have emerged as powerful and versatile glycan analogues for the investigation of cellular signal transduction. In this study, a layer of the glycopolymer-brush (GlyB) interface was functionalized on the surface of gold substrates. In order to enhance the capability and accessibility of this transducer interface, a combined protocol of copper(0)-mediated living radical polymerization (Cu(0)-LRP) with subsequent "CuAAC" click reaction was utilized to synthesize a set of novel glycopolymer precursors with a tunable scaffold structure and pyranose ligands. The resulting glycopolymer exhibited a fine-tuned molecular weight with a minor dispersity of 1.27. Through surface plasmon resonance (SPR) analysis, various GlyB interfaces exhibiting different saccharide moieties (glucose, mannose, and galactose) were examined to study their adhesion or antiadhesion potential toward three types of proteins, concanavalin A, bovine serum albumin, and peanut agglutinin (PNA). The strong affinity between poly(galactose) and PNA was further employed to construct a proof-of-concept aggregation-mediated sensing system. This minimal naked-eye sensor that consisted of only two substances, namely, gold nanoparticles and glycopolymers, was characterized and tested for its potential in protein quantification.

This study describes new mechanistic insights in the sequential polyassociation of streptavidin with biotinylated poly(ethyleneimine) glycopolymers and biotinylated PEGylated folic acid components for the preparation of biohybrid structures (BHS) for controlled targeting experiments. Characterization of the BHS revealed that during the formation and postfunctionalization of BHS, reversible dissociation and reassociation processes occur. The BHS are stable over weeks after finalizing the equilibrium-driven polyassociation process. Cellular uptake studies showed that this sequential polyassociation involving biotinylated PEGylated folic acid components does not lead to enhanced cellular uptake of the resulting BHS. In contrast, polyplexes, containing small interfering RNA and bioconjugates (1:1 molar ratio between biotinylated glycopolymer and monomeric streptavidin-lectin fusion protein), enabled us to control the targeting of tumor cells as revealed by knockdown of the tumor-associated protein survivin. Overall, this study demonstrates the high potential of (networklike) streptavidin-biotin interactions with a dynamic character in the formation of complex BHS and extracellular matrix materials.

In the mucosal epithelium, the cellular glycocalyx can project tens to hundreds of nanometers into the extracellular space, erecting a physical barrier that provides protective functions, mediates the exchange of nutrients and regulates cellular interactions. Little is understood about how the physical properties of the mucosal glycocalyx influence molecular recognition at the cellular boundary. Here, we report the synthesis of PEG-based glycopolymers with tunable glycan composition, which approximate the extended architecture of mucin glycoproteins, and tether them to the plasma membranes of red blood cells (RBC) to construct an artificial mucin brush-like glycocalyx. We evaluated the association of two lectins, ConA and SNA, with their endogenous glycan ligands on the surface of the remodelled cells. The extended glycocalyx provided protection against agglutination of RBCs by both lectins; however, the rate and magnitude of ConA binding were attenuated to a greater degree in the presence of the glycopolymer spectators compared to those measured for SNA. The different sensitivity of ConA and SNA to glycocalyx crowding likely arises from the distinct presentation of their mannoside and sialoside receptors, respectively, within the native RBC glycocalyx.

In this study, a linear glycopolymer-gadolinium conjugate (pGAEMA-DOTA-Gd) was prepared via the reversible addition fragmentation chain transfer (RAFT) polymerization. In addition, a crosslinked polymer-gadolinium conjugate (Crosslinked pGAEMA-DOTA-Gd) was prepared via a two-step RAFT polymerization approach, and its core was composed of the biodegradable oligopeptide GFLG. The features of the two glycopolymer-gadolinium conjugates as highly efficient and safe nanoscale contrast agents were discussed. These two glycopolymer-DOTA-Gd conjugates have aqueous dynamic particle sizes of 4.8 nm and 21.3 nm with neutral charges. Longitudinal relaxivity (r1) of these two glycopolymer-gadolinium conjugates were three to four times higher than that of clinical agent DTPA-Gd. Animal studies showed that pGAEMA-DOTA-Gd and Crosslinked pGAEMA-DOTA-Gd demonstrated higher signal intensity and the relative change in T1 value (ΔT1) in mouse liver and kidney, and prolonged blood circulation time compared to DTPA-Gd. Notably, the performance of the core-crosslinked glycopolymer conjugate was better than that of the linear polymer. Inductively coupled plasma mass spectrometry (ICP-MS) results showed that polymeric contrast agents, especially the crosslinked one, showed higher aggregation in mouse liver and kidney, and were mainly excreted through renal routes eventually. In vitro and in vivo toxicity studies in healthy mice including cytotoxicity, blood compatibility and systemic toxicity indicated the absence of significant toxicity. Therefore, the prepared glycopolymer-DOTA-Gd conjugates may have significant potential as highly efficient and safe nanoscale MRI contrast agents.

Burkholderia cepacia complex (Bcc) lung infections in cystic fibrosis (CF) patients are often associated with a steady decline in lung function and death. The formation of biofilms and inherent multidrug resistance are virulence factors associated with Bcc infection and contribute to increased risk of mortality in CF patients., Burkholderia cepacia complex (Bcc) lung infections in cystic fibrosis (CF) patients are often associated with a steady decline in lung function and death. The formation of biofilms and inherent multidrug resistance are virulence factors associated with Bcc infection and contribute to increased risk of mortality in CF patients. New therapeutic strategies targeting bacterial biofilms are anticipated to enhance antibiotic penetration and facilitate resolution of infection. Poly (acetyl, arginyl) glucosamine (PAAG) is a cationic glycopolymer therapeutic being developed to directly target biofilm integrity. In this study, 13 isolates from 7 species were examined, including Burkholderia multivorans, Burkholderia cenocepacia, Burkholderia gladioli, Burkholderia dolosa, Burkholderia vietnamiensis, and B. cepacia. These isolates were selected for their resistance to standard clinical antibiotics and their ability to form biofilms in vitro. Biofilm biomass was quantitated using static tissue culture plate (TCP) biofilm methods and a minimum biofilm eradication concentration (MBEC) assay. Confocal laser scanning microscopy (CLSM) visualized biofilm removal by PAAG during treatment. Both TCP and MBEC methods demonstrated a significant dose-dependent relationship with regard to biofilm removal by 50 to 200 μg/ml PAAG following a 1-h treatment (P