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Successful synthesis of glyconanoparticles has attracted much attention due to their various biointeractive capabilities, but it is still a challenge to understand different single-cell responses to exogenous particles among cell populations. Herein, we designed polyaniline-containing galactosylated gold nanoparticles (Au@PGlyco NPs) via in situ polymerization of ortho-nitrophenyl-β-galactoside assisted by Au nucleation. The nanogold-carrying polyaniline block produced electromagnetic enhancement in surface-enhanced Raman scattering (SERS). The underlying polymerization mechanism of ortho-nitrophenyl compounds via the formation of Au nanoparticles was investigated. Depending on how the galactoside moiety reacted with β-galactosidase derived from bacteria, the Au@PGlyco NPs-mediated SERS biosensor could detect low amounts of bacteria (∼1 × 102 CFU/mL). In addition, a high accumulation of Au@PGlyco NPs mediated the immune response of tumor-associated M2 macrophages to the immunogenic M1 macrophage transition, which was elicited by reactive oxygen levels biostimulation using single-cell SERS-combined fluorescence imaging. Our study suggested that Au@PGlyco NPs may serve as a biosensing platform with the labeling capacity on galactose-binding receptors expressed cell and immune regulation.

Antibiotic-resistant bacteria contamination in environments imposes great threats to human life health. This research aims to develop novel targeted antibacterial biochars for achieving high selectivity to kill pathogenic Escherichia coli (E. coli). The glycopolymer N-halamine-modified biochars (i.e., BCPMA-Cl) were synthesized by the modification of biochars with poly[2-(methacrylamido) glucopyranose-co-acrylamide] (P(MAG-co-AM), followed by chlorination treatment. Based on the results of FTIR, turbidity, XPS, and UV–vis, BCPMA-Cl was successfully synthesized and demonstrated to be able to eliminate Staphylococcus aureus (S. aureus) and E. coli. Especially, BCPMA-Cl possessed extremely potent to specific-killing 104 CFU∙ml−1 of E. coli with lower hemolytic activity (

Rapid diagnosis and vaccine development are critical to prevent the threat posed by viruses. However, rapid tests, such as colloidal gold assays, yield false-negative results due to the low quantities of viruses; moreover, conventional virus purification, including ultracentrifugation and nanofiltration, is multistep and time-consuming, which limits laboratory research and commercial development of viral vaccines. A rapid virus enrichment and purification technique will improve clinical diagnosis sensitivity and simplify vaccine production. Hence, we developed the surface-glycosylated microbeads (glycobeads) featuring chemically synthetic glycoclusters and reversible linkers to selectively capture the influenza virus. The surface plasmon resonance (SPR) evaluation indicated broad spectrum affinity of S-linked glycosides to various influenza viruses. The magnetic glycobeads were integrated into clinical rapid diagnosis, leading to a 30-fold lower limit of detection. Additionally, the captured viruses can be released under physiological conditions, delivering purified viruses with >50% recovery and without decreasing their native infectivity. Notably, this glycobead platform will facilitate the sensitive detection and continuous one-step purification of the target virus that contributes to future vaccine production.

We report a novel glycan array architecture that binds the mannose-specific glycan binding protein, concanavalin A (ConA), with sub-femtomolar avidity. A new radical photopolymerization developed specifically for this application combines the grafted-from thiol-(meth)acrylate polymerization with thiol-ene chemistry to graft glycans to the growing polymer brushes. The propagation of the brushes was studied by carrying out this grafted-to/grafted-from radical photopolymerization (GTGFRP) at >400 different conditions using hypersurface photolithography, a printing strategy that substantially accelerates reaction discovery and optimization on surfaces. The effect of brush height and the grafting density of mannosides on the binding of ConA to the brushes was studied systematically, and we found that multivalent and cooperative binding account for the unprecedented sensitivity of the GTGFRP brushes. This study further demonstrates the ease with which new chemistry can be tailored for an application as a result of the advantages of hypersurface photolithography.

Glycopolymer-based drugs for immunotherapy have attracted increasing attention because the affinity between glycans and proteins plays an important role in immune responses. Previous studies indicate that the polymer chain length influences the affinity. In the studies on enhancing the immune response by glycans, it is found that both oligosaccharides and long-chain glycopolymers work well. However, there is a lack of systematic studies on the immune enhancement effect and the binding ability of oligomers and polymers to immune-related proteins. In this paper, to study the influence of the chain length, glycopolymers based on N-acetylglucosamine with different chain lengths were synthesized, and their interaction with immune-related proteins and their effect on dendritic cell maturation were evaluated. It was proved that compared with l-glycopolymers (degree of polymerization (DP) > 20), s-glycopolymers (DP < 20) showed better binding ability to the dendritic cell-specific ICAM-3-grabbing nonintegrin protein and the toll-like receptor 4 and myeloid differentiation factor 2 complex protein by quartz crystal microbalance and molecular docking simulation. When the total sugar unit amounts are equal, s-glycopolymers are proved to be superior in promoting dendritic cell maturation by detecting the expression level of CD80 and CD86 on the surface of dendritic cells. Through the combination of experimental characterization and theoretical simulation, a deep look into the interaction between immune-related proteins and glycopolymers with different chain lengths is helpful to improve the understanding of the immune-related interactions and provides a good theoretical basis for the design of new glycopolymer-based immune drugs.

Multivalent antibody-recruiting glycopolymers (MARGs) composed of hyaluronic acid (HA) grafted with multiple copies of dinitrophenol (DNP) were developed for targeted cancer immunotherapy. Structure-activity studies demonstrated that the MARGs were able to specifically recognize CD44-positive cancer cells and displayed remarkable antibody-recruiting capacities and tumor cell killing activities dependent on the introduced multivalent effect and the length of PEG linker. One of the MARGs, HA-[PEG3 -DNP]8 , showed the best capacity for clustering anti-DNP antibodies onto CD44-positive cancer cells and displayed potent in vitro anti-cancer activity by triggering complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, we found that HA-[PEG3 -DNP]8 significantly inhibited the xenograft tumor growth of Babl/c nude mice bearing triple negative breast cancer cells, while it did not cause detectable histological cytotoxicity. Given the easy access of this type of natural glycopolymer and the practical synthesis approach, these MARGs provide promising immunotherapeutics for cancer immunotherapy.

Presence of the cell wall glycopolymer rhamnan was established for members of the genus Curtobacterium (family Microbacteriaceae) by using chemical and NMR spectroscopic methods. The rhamnan with the repeating unit, →2)-α-L-Rhap-(1→3)-α-L-Rhap-(1→, was found in C. flaccumfaciens pv. flaccumfaciens VKM Ас-1923T, C. flaccumfaciens pv. poinsettiae VKM Ас-1924T, C. pusillum VKM Ac-2099T, C. herbarum VKM Ac-2512T, and Curtobacterium sp. VKM Ac-1811. Each of the studied strains also contained a second, acidic phosphate-free polysaccharide. NMR spectra of these polysaccharides differed, indicating the structural differences. Cell wall hydrolysates of all studied strains were found to contain rhamnose, mannose, glucose, galactose, and glucosamine. Further research will facilitate more detailed characterization of the composition of cell wall glycopolymers in Curtobacterium species, as well as evaluation of their taxonomic significance. The data on the polymer structure will contribute to understanding of the mechanisms of colonization and infection of higher organisms by Curtobacterium species and bacterial interaction in microbial communities and with abiotic environmental objects.

Conventional polystyrene (PS) monoliths are rarely used for separation of biomacromolecules due to their heterogeneous skeletons and hydrophobic surfaces. In this work, high-permeable and bimodal o...

Thermoresponsive polymer vesicles are promising drug-delivery carriers because of their ability to release cargo in a controlled manner. However, the process of thermoresponsive vesicle disassembly has attracted only limited attention to date, and the details remain elusive. Herein, we report using small-angle X-ray scattering and confocal laser scanning microscopy for in situ observation of the disassembly process during the cooling of thermoresponsive maltopentaose-b-poly(propylene oxide) polymer vesicle solutions. Notably, vesicle collapse mainly involves three discrete steps, not a concerted process. We also demonstrate that protein-loaded vesicles can be triggered to release their cargo upon cooling and that released protein retains its enzymatic activity. This study can thus provide a basis for generating guidelines for using thermoresponsive polymer vesicles in the triggered release of cargo and facilitating the development of new thermoresponsive materials based on poly(propylene oxide). The real-time structural changes of thermoresponsive polymer vesicles upon cooling were investigated by small-angle X-ray scattering and confocal laser scanning microscopy. The disassembly process of the vesicles consists of multiple steps: 1) pore formation, 2) opening and shrinkage of the membrane, and 3) dissolving in the solvent. We also demonstrated that the vesicles can be used as compartments for the controlled release of proteins. This study provides the basis for the mechanism of the disassembly process of thermoresponsive vesicles and a guideline for their use as controlled-release medical devices.

We report the synthesis of an end-to-end protein–glycopolymer conjugate, namely, site-specific modification of recombinant thrombomodulin at the C-terminus with a chain-end-functionalized glycopolymer. Thrombomodulin (TM) is an endothelial membrane glycoprotein that acts as a major cofactor in the protein C anticoagulant pathway. To closely mimic the glycoprotein structural feature of native TM, we proposed a site-specific glyco-engineering of recombinant TM with a glycopolymer. Briefly, recombinant TM containing the epidermal growth factor (EGF)-like domains 4, 5, and 6 (rTM456) and a C-terminal azidohomoalanine was modified with a dibenzylcyclooctyne (DBCO) chain-end-functionalized glycopolymer via copper-free click chemistry to afford the end-to-end TM–glycopolymer conjugate. The TM glycoconjugation was confirmed with SDS-PAGE, Western blot, and protein C activation assay, respectively. The reported site-specific end-to-end protein glycopolymer conjugation approach facilitates uniform glycoconjugate fo...

We introduce the light-induced collapse of single glycopolymer chains in water generating fluorescent glyco single-chain nanoparticles (SCNPs) and their subsequent functionalization onto nanodiamonds. The glycopolymer precursors are prepared by polymerizing an acetylated mannose-based methacrylate monomer followed by a deprotection and postpolymerization functionalization step, introducing profluorescent photoactive tetrazole groups and furan-protected maleimide moieties. Subsequent UV irradiation in highly diluted aqueous solution triggers intramolecular tetrazole-mediated cycloadditions, yielding glyco SCNPs featuring fluorescence as well as lectin binding properties. The obtained SCNPs are coated onto nanodiamonds by adsorption, and the obtained hybrid nanoparticles are in depth characterized in terms of size, functionality, and bioactivity. Different coating densities are achieved by altering the SCNP concentration. The prepared nanoparticles are nontoxic in mouse RAW 264.7 macrophages. Furthermore, the fluorescence of the SCNPs can be exploited to image the SCNP-coated nanodiamonds in macrophage cells via confocal fluorescence microscopy.

Sugar regioisomerism (glycosidic linkage on different hydroxyl groups of the same sugar) widely exists in various polysaccharides and glycans with a significant contribution to their biological functions. However, the effects of this regioisomersim in glycopolymers and their self-assembled nanoparticles on such functions were almost not investigated previously. In this paper, this regioisomersim effect is studied for self-assembled nanoparticles NP-1-Gal and NP-6-Gal from triblock copolymers carrying different constitutional isomers of the pendent sugar species (1 and 6 denote the glycosidic linkage from the anomeric position and 6 position of the galactose unit, respectively). NP-1-Gal shows strong binding to lectins of Peanut (Arachis hypogea) agglutinin (PNA) and Erythrina cristagalli agglutinin (ECA), while NP-6-Gal does not. More importantly, they show binding behavior similar to the asialoglycoprotein receptor (ASGPR) but different internalization pathways in the Hep G2 cell after ASGPR-mediated end...

A highly porous cryogel is prepared and subsequently functionalized with an atom transfer radical polymerization (ATRP) initiator at the surface. Two new glycomonomers are introduced, which possess deprotected mannose as well as glucose moieties. These are copolymerized with N-isopropylacrylamide (NiPAm) from the cryogel surface, providing a highly hydrophilic porous material, which is characterized by SEM, FT-IR spectroscopy, and NMR spectroscopy. This functionalized support can be applied for affinity chromatography of whole cells owing to the high pore space and diameter. Such an application is exemplified by investigating the ability to capture Escherichia coli bacteria, revealing selective binding interactions of the bacteria with the mannose glycopolymer-functionalized cryogel surface. Thus, the presented glycopolymer-cryogel represents a promising material for affinity chromatography or enrichment of cells.

The facile and efficient functionalization of thermoresponsive polymers based on sequential, reversible thiol-exchange reactions is reported. Well-defined dithiomaleimide-containing polymers have been synthesized via Cu(0)-mediated SET-LRP and characterized by 1H NMR and size exclusion chromatography (SEC). The resulting thermosensitive copolymers were subsequently reacted with various thiols to demonstrate the applicability of the strategy, and the thiol-exchange reaction was found to be very fast and efficient. The cloud point of the prepared copolymers can be continually and reversibly tuned, and desirable functionality can be dynamically exchanged upon sequential addition of functional thiol reagents. Through the substitution by thioglucose, an ON-to-OFF switch for fluorescence of the copolymers along with the generation of a glycopolymer was achieved.

Herein, we demonstrate the reversible addition–fragmentation chain transfer (RAFT) synthesis of an adamantane-conjugated glycopolymer, poly(2-methacrylamido-2-deoxy glucopyranose) (Ad-pMAG), as a hydrophilic coating to promote colloidal stability of click cluster-pDNA complexes in biological media. The Ad-pMAG is assembled via noncovalent interactions through inclusion complex formation between adamantane (Ad) and the β-cyclodextrin (βCD) core of the click cluster/pDNA and then further assembled with plasmid DNA to form polyplexes. Ad-pMAG incorporation was favorable over Ad-poly(ethylene glycol) (Ad-PEG) due to the enhanced colloidal stability of the click cluster/pDNA polyplex under physiological salt conditions at high N/P ratios. Interestingly, the uptake and reporter gene expression with polyplexes coated with the Ad-pMAG was much lower in HeLa cells than that observed with two glioma cell lines (U87 and U251 cells) in vitro, possibly indicating some delivery specificity.

Glycopolymers that can mimic natural glycosaminoglycan, such as heparin, have shown great potentials in inhibition of cancer metastasis. In the current work, a novel series of brush-like glycopolymers (BGPs) with simultaneous functionalization of various monosaccharide or disaccharide compositions have been synthesized through a new grafting-polymerization strategy, in order to mimic the activities of both heparin and P-selectin ligand PSGL-1. In the subsequent in vitro assays of antiadhesion, platelets activation, heparanase inhibition, and so on, BGP-SFH, as one of the BGPs with the composition of the combined three sugar units, sialic acids, fucoses, and heparin disaccharides, showed the highest antimetastasis ability, similar to its prototype heparin. Moreover, in a mouse metastatic melanoma model, the BGP-SFH also inhibited B16 cell metastasis effectively. Thus, the current work not only demonstrated a type of promising antimetastasis glycopolymer BGPs, but also illustrated an easy synthetic approach to multifunctionalized glycopolymers, leading to potential applications for broader biomedical research.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer., Highlights • A cathepsin B-responsive theranostic nanomedicine (glycopolymer-PTX-DOTA-Gd) based on a branched glycopolymer was prepared. • Glycopolymer-PTX-DOTA-Gd can be specifically degradated and release drug at tumor enviornment. • Glycopolymer-PTX-DOTA-Gd enhance the contrast of magnetic resonance imaging (MRI) at tumor sites. • The nanomedicine have good biocompatibility, excellent tumor targeting and anti-tumor efficacy., Graphical abstract Cathepsin B-responsive biodegradable branched glycopolymer-based prodrug was designed and prepared as theranostic nanomedicine for cancer treatments, resulting in significantly enhanced therapeutic indexes and strengthened contrast of magnetic resonance imaging (MRI) at tumor sites.Image 1

The rapid rise in research interest in carbohydrate-based polymers is undoubtedly due to the nontoxic nature of such materials in an in vivo environment and the versatile roles that the polymers can play in cellular functions. Such polymers have served as therapeutic tools for drug delivery, including antigens, proteins, and genes, as well as diagnostic devices. Our focus in the first half of this Review is on synthetic methods based on ring-opening polymerization and enzyme-catalyzed polymerization, along with controlled radical polymerization. In the second half of this Review, sugar-based polymers are discussed on the basis of their remarkable success in competitive receptor binding, as multifunctional nanocarriers of targeting inhibitors for cancer treatment, in genome-editing delivery, in immunotherapy based on endogenous antibody recruitment, and in treatment of respiratory diseases, including influenza A. Particular emphasis is put on the synthesis and biopharmaceutical applications of sugar-based polymers published in the most recent 5 years. A noticeable attribute of carbohydrate-based polymers is that the sugar-receptor interactions can be facilitated by the cooperative effect of multiple sugar units. Their diversified topology and structures will drive the development of new synthetic strategies and bring about important applications, including coronavirus-related drug therapy.

The "carbohydrate module method" is a promising approach for oligosaccharide mimetics using polymeric materials. However, it is difficult to predict the optimal structure for a particular oligosaccharide mimetic, and an efficient strategy for the synthesis and evaluation of glycopolymers is desirable. In this study, a screening of glycopolymers for the "carbohydrate module method" by a combination of photoinduced electron/energy transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization and surface plasmon resonance imaging (SPRI) is demonstrated. The facile and fast screening of synthetic glycomimetics was achieved, and the glycopolymer with the optimal structure as a GM1 mimetic strongly interacted with the cholera toxin B subunit.

Heterogeneous glycopolymers have received significant interest in the past few years due to their potential properties in enhancing the molecular recognition abilities toward a specific receptor. However, there are limited reports on correlating the type of non-binding sugar residue with its synergistic effects on the affinity to lectin in a complex hetero-multivalent system. To shed more light on the heterogeneity in carbohydrate–lectin recognition, we have designed heterogeneous dendronized glycopolymers presenting α-mannose, β-galactose, and/or β-glucose residues in the side chains, which are synthesized by post-polymerization modification of activated PFPA ester precursor polymers. Tri-functionalized dendronized amines bearing different sugar motifs have been synthesized by a gradient CuAAC reaction, which could serve as a platform for achieving multi-heterogeneous sugar units in a controlled manner. ITC measurements showed that all heterogeneous dendronized glycopolymers demonstrate higher affinities towards Con A as the model lectin compared to their homogeneous dendronized analogues presenting the same number of binding α-mannose units, which further confirmed that the presence of a β-glucose or β-galactose unit as a non-binding sugar motif could produce a synergistic effect on the binding of an α-mannose unit to Con A. Further systematic studies on the heterogeneity in glycopolymer–lectin binding revealed that β-galactose as a non-binding sugar unit could generate a higher synergistic effect on binding with Con A than the β-glucose unit. More intriguingly, ABC-type dendronized glycopolymers bearing α-mannose, β-galactose, and β-glucose residues show higher affinities towards Con A than their dendronized analogues that present only one type of non-binding sugar unit due to a co-synergistic effect. The stronger synergistic effect of this heterogeneity on the interaction between the ABC-type dendronized glycopolymer and Con A may be expressed as the synergism of the secondary and tertiary sugar units that promote the dynamic movement of lectin from the glycopolymer to glycopolymer epitopes. These results provide more evidence that heterogeneity plays a crucial role in glycopolymer–lectin binding.

Poly(vinylbiphenyl)s bearing glycoside ligands at the side chains were prepared using the Suzuku coupling reaction. Effects of glycoside reactant concentration, halide species, glycoside species, and catalyst species on the incorporation of glycoside ligand into the polymer were investigated. The obtained glycopolymers exhibited specific binding to proteins corresponding to the glycoside ligands. In addition, the biphenyl spacers formed by the Suzuki coupling reaction in the glycopolymer were fluorescent, whereas the polymer precursor was not.

Detection of vaccine (adjuvant and antigen) is crucial for the fundamental studies of immunotherapy. In this work, the catechol-containing glycopolymer obtained by sunlight-induced RAFT polymerization was first designed to generate glycoadjuvant@AuNPs. Then, a simple and general self-assembled technique, catechol-driven self-assembly (CDSA), was developed to fabricate AuNP-based glycoadjuvant patterns, regardless of the size, shape and synthetic method of AuNPs. More importantly, highly ordered glycoadjuvant patterns could be easily formed by catechol-driven self-assembly under confinement, which exhibit a higher SERS signal amplification ability for the detection of carbohydrates (glycoadjuvant).

Polysaccharides are polymeric chains comprised of saccharides connected through glycosidic bonds that have important biological functions, such as energy storage, structure, and cell signaling. Although polysaccharides are ubiquitous in nature, there are limited tools for examining their roles due to the complexity of polysaccharide synthesis. In order to synthesize well-defined polysaccharides, selective protection/deprotection techniques are employed that require tedious purification at each intermediate. In order to facilitate the creation of high molecular weight saccharide-bearing polymers, glycopolymers can be created as an alternative. Glycopolymers emulate the interactions observed in natural polysaccharides through the use of synthetic analogues.Glycopolymers are synthetic polymers that present saccharide side groups. Although glycopolymers have been produced with control over saccharide identity and molecular weight, only limited investigations have been conducted to incorporate cationic charge or control branched architecture. Currently, cationic charge is incorporated through the copolymerization of cationic monomers with glycomonomers, but the inclusion of cationic monomers has led to increased cytotoxicity. There have been no examples of glycopolymers utilizing the inherent charge available on amino-sugars, such as glucosamine. In addition, branched glycopolymers have previously been studied using atom-transfer radical polymerization, but the polymerization technique is incompatible with amine-containing monomers and requires removal of the copper catalyst. Reversible addition-fragmentation chain transfer (RAFT) polymerization is an alternative technique for glycopolymer synthesis, but branching has only been introduced using crosslinkers that result in gelation at high degrees of incorporation. To address these limitations, new cationic glycomonomers and RAFT branching units have been synthesized.Using these new tools, in addition to those currently available for glycopolymer synthesis, a number of biomedical applications were investigated: bacterial attachment on glycopolymer-modified surfaces, lectin interaction with 3D constructs that present saccharides at different densities, antibacterial activity of a cationic glycopolymer, and potential usage of a cationic glycopolymer in gene transfection.Using a set of four glycomonomers synthesized from glucose, galactose, mannose, and N acetyl glucosamine, glycopolymer of various saccharide identities were polymerized via RAFT polymerization and conjugated to gold surfaces to investigate the attachment of Shewanella oneidensis and Vibrio cholerae. Polymeric mannose was seen to encourage significantly more attachment than monomeric mannose, polymeric galactose, and polymeric N acetyl glucosamine.Using a RAFT branching unit, amphiphilic glycopolymers were polymerized and self-assembled into nanoparticles with control over the surface saccharide density without affecting size and morphology. The nanoparticles with increased branching bound more lectin compared to nanoparticles without branching and glycopolymers in solution.Using a cationic glycomonomer, a chitosan-mimic was polymerized and investigated for similarities in bioactivity. In antibacterial studies, the cationic glycopolymer closely mimicked the ability of chitosan to inhibit bacterial growth above a threshold molecular weight. Unlike chitosan, the glycopolymer was also soluble in neutral and basic buffer and maintained its ability to inhibit bacterial growth. As a transfection agent, the glycopolymer was able to induce gene expression with less cytotoxicity than poly(ethylenimine), the standard synthetic transfection agent, but with more cytotoxicity than chitosan. With optimization, the chitosan-mimic can be an efficient transfection agent with low cytotoxicity.We have described the addition of new synthetic tools for creating cationic glycopolymers and hyperbranched glycopolymers. The applications presented demonstrate the importance of control over saccharide identity, branching, and charge in glycomimetic systems and can be applied to the design of new therapeutics and devices.

A one-pot strategy was applied to synchronize enzymatic monomer transformation with reversible addition fragmentation chain transfer (RAFT) polymerization for the synthesis of glycopolymers with highly branched gradient architectures. Also, the linear analogues, block glycopolymers, and gradient glycopolymers were also synthesized for comparison. The binding ability of glycopolymers toward bacteria was then studied by optical density (OD) test, confocal laser scanning microscopy (CLSM), and quartz crystal microbalance with dissipation (QCM-D). The results show that the highly branched gradient glycopolymers have the most remarkable bacteria-binding ability compared with the two linear analogues, gradient glycopolymers, and block glycopolymers. The highly branched glycopolymers were further used as inhibitors in the anti-infection test, demonstrating a significant inhibitory effect on preventing bacteria from infecting the cells.