Synthetic carbohydrate ligands -also widely known as glycopolymers -are known to undergo numerous recognition events when interacting with their corresponding lectins. Interactions are greatly enhanced due to the multivalent character displayed by the large number of repeating carbohydrate units along the polymers (pendant glycopolymers); therefore, resulting what is called the ''glycocluster effect''. Moreover, the strength and the availability of these multivalent recognitions can be tuned via the architecture of the glycopolymers. Hence, understanding the mechanistic interactions between the types of lectins (plant, animal, toxin and bacteria) with their synthetic ligands is crucial. This review focuses on the synthesis of pendant glycopolymers via various synthetic pathways (free radical polymerization, NMP, RAFT, ATRP, cyanoxyl mediated polymerization, ROP, ROMP and post-polymerization modification) and their interactions with their respectively lectins.

The preparation of poly(2-(2′,3′,4′,6′-tetra-O-acetyl-β-d-galactosyloxy)ethyl methacrylate-co-styrene) (P(AcGalEMA-co-S)) glycopolymer was performed via nitroxide-mediated polymerization using a methacrylic acid-based alkoxyamine with N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) (SG1) nitroxide as mediating agent. In the presence of a low proportion of styrene, the polymerization of the glycomonomer was conducted in a controlled fashion at 85 °C. The synthesis of the diblock copolymers was investigated via two routes by using either P(AcGalEMA-co-S) or polystyrene macroinitiators capped with SG1 nitroxide to yield P(AcGalEMA-co-S)-b-PS and PS-b-P(AcGalEMA-co-S), respectively. The AcGalEMA moieties on the diblock copolymer were deacetylated to afford carbohydrate-based amphiphilic diblock copolymer, polystyrene-block-poly(2-(β-d-galactosyloxy)ethyl methacrylate-co-styrene) (PS-b-P(GalEMA-co-S)). The self-assembling properties of PS-b-P(GalEMA-co-S) amphiphilic diblock copolymers were thoroughly exploited to obtain micellar structures and porous films. Lectin binding assays were conducted using the UV−vis spectroscopy and dynamic light scattering to test the biofunctionality of the β-galactose moieties with peanut agglutinin (PNA) on the micelles. The polymer was used to prepare honeycomb structured porous films with bioactivity. Fluorescent PNA was eventually conjugated with the sugar moieties on the porous films. Most protein was conjugated to glycopolymer inside the pore, demonstrating that this procedure can be a simple route to pattern proteins onto surfaces.

Glyco-particles bearing glucose units have been prepared via a one-step controlled/living ab initio cross-linking emulsion polymerization of styrene based on self-assembly via a glucose RAFTstab (reversible addition−fragmentation chain transfer colloidal stabilizer). The RAFTstab was synthesized from the monomer 2-(methacrylamido)glucopyranose (MAG) and the hydrophobic trithiocarbonate RAFT agent S-methoxycarbonylphenylmethyl dodecyltrithiocarbonate (MCPDT). In order to obtain glyco-particles stable for biomedical applications, a degradable bis(2-acryloyloxyethyl) disulfide cross-linker (disulfide diacrylate, DSDA) was employed in the emulsion polymerization. The cross-linked glyco-particles were stable in N,N -dimethylacetamide (DMAc), in contrast to the corresponding non-cross-linked glyco-particles which disintegrate to form linear glycopolymers in solution. The cross-linked particles underwent reductive degradation into the constituent linear (primary) chains upon treatment with 1,4-dithiothreitol (DDT). The bioactivity of the glucose moieties on the surface of the particles was examined using two classes of lectins, namely plant lectin (Concanavalin A, Canavalia ensiformis) and bacteria lectin (fimH, from Escherichia coli). Successful binding was demonstrated, thus illustrating that these particles have potential as “smart” materials in biological systems.

Hollow poly(6-O-acryloyl-alpha-D-galactopyranose) (PAGP) nanospheres were prepared in a facile manner using the RAFT (reversible addition fragmentation chain transfer) process. Initially, an amphiphilic block copolymer, poly(lactide)-block-poly(6-O-acryloyl-alpha-D-galactopyranose) (PLA-b-PAGP), was synthesized using a poly(lactide) (PLA) macroRAFT agent. It was attained in high yields and displayed low PDI values. The block copolymers self-assembled in aqueous solution to form micelles with pendent galactose moieties covering the surface. By using hexandiol diacrylate the micelles were cross-linked at the nexus of the copolymer, creating stable aggregates. Aminolysis with hexylamine allowed the removal of the PLA core without any detrimental effect on the glycopolymer units to produce hollow nanocages. Characterization of these hollow "sugar balls" with transmission electron microscopy (TEM) showed the cross-linked micelles with a central void due to the removal of the hydrophobic block. These micelles are advantageous in drug delivery applications, especially those involving the liver, thanks to the pendent galactose functionalities covering the surfaces of the nanocages.

The present communication explores a novel avenue to glycopolymer-block-poly(vinyl acetate) polymers by a combination of reversible addition fragmentation chain transfer (RAFT) chemistry and Huisgen 1,3-dipolar cycloaddition (i.e., so-called ‘click’ chemistry) under mild reaction conditions. Such block copolymers are—because of the strongly disparate reactivity of the two monomers—otherwise not obtainable. Poly(vinyl acetate) that has an azide end group (Mn 6800 g mol–1, PDI 1.15) was treated with poly(6-O-methacryloyl mannose) (Mn 7600 g mol–1, PDI 1.11) in the presence of 1,8-diaza[5,4,0]bicycloundec-7-ene and copper(i) iodide. The resulting poly(vinyl acetate)-block-poly(6-O-methacryloyl mannose) had a number-average molecular weight of 15400 g mol–1 and a PDI of 1.48, which indicates that while the cycloaddition had occurred the resulting polymer distribution featured a considerable width. The resulting slightly amphiphilic block copolymer was subsequently investigated with regard to its self-assembly in aqueous solution. Dynamic light scattering studies indicated a hydrodynamic diameter of close to 200 nm. Transmission electron microscopy studies indicate the formation of rods as well as spheres with transitions between these two phases. However, the segregation between core and shell in the spheres is not pronounced; such behaviour is expected for weakly amphiphilic block copolymers.

Stable and surface‐modified films with regular porous arrays were created by crosslinking honeycomb structured porous films prepared via breath figures from poly(styrene‐co‐maleic anhydride). The formation of open or closed pores of the films was controlled by the addition of a polyion complex. Subsequent crosslinking of the films with 1,8‐diaminooctane led to films, which maintain their structure in solvents. In addition, excess amino functionality after crosslinking allowed the attachment of RAFT agent, 3‐benzylsulfanyl thiocarbonyl sulfanylpropionic acid, for the controlled surface polymerization of N‐isopropyl acrylamide (NIPAAm) and N‐acryloyl glucosamine (AGA). The attachment of thermo‐responsive glycopolymers onto the honeycomb structured porous films was confirmed using contact angle measurements and confocal fluorescence microscopy. Cleavage of surface anchored polymers via aminolysis revealed that the molecular weights of the surface grafted chains are significantly larger than the molecular weight of the chains generated in solution. The honeycomb structured porous films with their grafted PNIPAAm‐ran‐PAGA polymer chains showed selective recognition of Concanavalin A (ConA). Below the lower critical solution temperature (LCST) of the surface, the conjugation is switched off, while above the LCST the surface grafted glucose moieties bind strongly to ConA. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3440–3455, 2010

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