Cyanoxyl-mediated Free-radical Polymerization Research Articles

Straightforward Synthesis of N-Glycan Polymers from Free Glycans via Cyanoxyl Free Radical-Mediated Polymerization.

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.

Synthesis of Chain-End Functionalized Glycopolymers via Cyanoxyl-Mediated Free Radical Polymerization (CMFRP).

Glycopolymers are often used as glyco-macroligands for biological research and biomedical applications in carbohydrate recognitions. Chain-end functionalized glycopolymers show more potential for practical applications, such as protein modification and solid-phase bioassays. In particular, the chain-end group allows for direct one-to-one attachment or facilitates site-specific and oriented immobilization onto solid surfaces. A series of derivatized arylamine initiators are used to generate chain-end functionalized glycopolymers by cyanoxyl-mediated free radical polymerization (CMFRP). Important features of this strategy include the capacity to produce polymers of low polydispersity (PDI <1.5) under aqueous conditions using unprotected monomers bearing a wide range of functional groups. In addition, it provides a one-pot method to synthesize α,ω-telechelic glycopolymers with derivatized arylamine at one site and O-cyanate at the other site. In the process, the capacity to orthogonally label glycopolymers or otherwise conjugate them to proteins and other molecules is greatly enhanced.

Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization.

The sulfated marine polysaccharide fucoidan has been reported to have health benefits ranging from antivirus and anticancer properties to modulation of high blood pressure. Hence, they could enhance the biological function of materials for biomedical applications. However, the incorporation of fucoidan into biomaterials has been difficult, possibly due to its complex structure and lack of suitable functional groups for covalent anchoring to biomaterials. We have developed an approach for a rapid synthesis of fucoidan-mimetic glycopolymer chains through cyanoxyl-mediated free-radical polymerization, a method suitable for chain-end functionalizing and subsequent linkage to biomaterials. The resulting sulfated and nonsulfated methacrylamido α-L-fucoside glycopolymers' fucoidan-mimetic properties were studied in HSV-1 infection and platelet activation assays. The sulfated glycopolymer showed similar properties to natural fucoidan in inducing platelet activation and inhibiting HSV-1 binding and entry to cells, thus indicating successful syntheses of fucoidan-mimetic glycopolymers.

Synthesis of Glycopolymers by Controlled Radical Polymerization Techniques and Their Applications

Natural saccharides are involved in numerous biological processes. It has been shown that these carbohydrates play a role in cell adhesion and proliferation, as well as protein stabilization, organization, and recognition. Certain carbohydrates also serve as receptors for viruses and bacteria. They are over expressed in diseases such as cancer. Hence, a lot of effort has been focused on mimicking these sugars. Polymers with pendent saccharide groups, also known as glycopolymers, are studied as oligo- and polysaccharide mimics. Controlled radical polymerization (CRP) techniques such as atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization, and nitroxide-mediated polymerization (NMP), as well as cyanoxyl-mediated free radical polymerization have allowed chemists to synthesize well-defined glycopolymers that, in some cases, have particular end-group functionalities. This review focuses on the synthesis of glycopolymers by these methods and the applications of glycopolymers as natural saccharide mimics.

Immobilized Sialyloligo-Macroligand and Its Protein Binding Specificity

We report a chemoenzymatic synthesis of chain-end functionalized sialyllactose-containing glycopolymers with different linkages and their oriented immobilization for glycoarray and SPR-based glyco-biosensor applications. Specifically, O-cyanate chain-end functionalized sialyllactose-containing glycopolymers were synthesized by enzymatic α2,3- and α2,6-sialylation of a lactose-containing glycopolymer that was synthesized by cyanoxyl-mediated free radical polymerization. (1)H NMR showed almost quantitative α2,3- and α2,6-sialylation. The O-cyanate chain-end functionalized sialyllactose-containing glycopolymers were printed onto amine-functionalized glass slides via isourea bond formation for glycoarray formation. Specific protein binding activity of the arrays was confirmed with α2,3- and α2,6-sialyl specific binding lectins together with inhibition assays. Further, immobilizing O-cyanate chain-end functionalized sialyllactose-containing glycopolymers onto amine-modified SPR chip via isourea bond formation afforded SPR-based glyco-biosensor, which showed specific binding activity for lectins and influenza viral hemagglutinins (HA). These sialyloligo-macroligand derived glycoarray and SPR-based glyco-biosensor are closely to mimic 3D nature presentation of sialyloligosaccharides and will provide important high-throughput tools for virus diagnosis and potential antiviral drug candidates screening applications.

Synthesis and Characterization of Oriented Glyco‐Capturing Macroligand

An oriented glyco-capturing macroligand was synthesized by site-specific immobilization of an O-cyanate chain-end-functionalized boronic acid containing polymer (boropolymer) onto an amine surface. The O-cyanate chain-end-functionalized boropolymer was synthesized by arylamine-initiated cyanoxyl-mediated free-radical polymerization in a one-pot fashion. The chain-end O-cyanate was confirmed by (13)C NMR spectroscopy. The specific carbohydrate-binding capacity of the boropolymer was evaluated by an alizarin red S assay. Oriented and covalent immobilization of the O-cyanate chain-end-functionalized boropolymer onto the amine-modified solid surfaces and its specific glyco-capturing capacity were confirmed by the quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques. The oriented multivalent glyco-capturing ligand can be used for efficient carbohydrate and glycoconjugate purification and identification, and thus is expected to constitute a core strategy of glycomics and glycoproteomics and carbohydrate-sensing applications.

Synthesis and characterization of biotin chain-end functionalized boronic acid-containing polymer (boropolymer) as functional glyco-affinity macroligand

A biotin chain-end functionalized boronic acid-containing polymer (biotin boropolymer) as an oriented glyco-affinity macroligand for efficient carbohydrate and glycoconjugate purification and identification application was described. Briefly, the biotin boropolymer was synthesized via a biotin derivated arylamine initiated cyanoxyl-mediated free-radical polymerization in one-pot fashion. The specific streptavidin binding capacity of biotin boropolymer was confirmed by streptavidin–HABA assay, while the specific carbohydrate binding capacity of biotin boropolymer was evaluated by Alizarin Red S binding assay. Efficient glyco-capturing followed by direct MALDI mass spectrometry identification of the captured carbohydrate was demonstrated by using magnetic bead functionalized with the biotin boropolymer via streptavidin/biotin interaction.

Facile synthesis of chain-end functionalized glycopolymers for site-specific bioconjugation.

A series of derivatized arylamine initiators were used to generate chain-end functionalized glycopolymers by cyanoxyl-mediated free-radical polymerization. Significant features of this strategy include the capacity to produce polymers of low polydispersity (PDI < 1.5) under aqueous conditions using unprotected monomers bearing a wide range of functional groups. In addition, the presence of a phenyl ring simplifies calculation of polymer saccharide content and molar mass by (1)H NMR. It is particularly noteworthy, however, that derivatized arylamine initiators in conjunction with the presence of a terminal cyanate group provide a convenient approach for synthesizing polymers with a variety of distinct functional groups at alpha and omega chain ends. In the process, the capacity to label glycopolymers or otherwise conjugate them to proteins or other molecules is greatly enhanced.

Cyanoxyl-mediated free-radical polymerization of acrylic acid: Its scope and limitations

This work examines the scope and limitations of the cyanoxyl (·OCN)-mediated free-radical polymerization of acrylic acid (AA) with respect to the criteria of livingness. Cyanoxyl persistent radicals were generated in situ through the reaction between arenediazonium salts (XC6H4NN⊕BF, where X is H, OCH3, Cl, or NO2) and sodium cyanate (NaOCN). This article thoroughly discusses the role played by such oxygen-centered radicals in the polymerization process; it particularly focuses on the influence of the concentration and nature of the diazonium salt, the solvent, and the temperature on features such as the variations of ln([M]0/[M]) versus time (where [M]0 is the initial monomer concentration and [M] is the monomer concentration), the number-average molar mass versus conversion, and the polydispersity versus conversion in cyanoxyl-mediated free-radical polymerizations of AA. Cyanoxyl-terminated samples were used as macroinitiators for the polymerization of methyl methacrylate to generate poly(acrylic acid)-b-poly(methyl methacrylate) block copolymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 519–533, 2005

Design and Synthesis of Biotin Chain-Terminated Glycopolymers for Surface Glycoengineering

Biotin chain-terminated glycopolymers were generated by cyanoxyl-mediated free-radical polymerization using a biotin-derivatized arylamine initiator with high conversion (75%) and low polydispersity (1.30). Streptavidin-biotinylated glycopolymer binding was verified by SDS-PAGE gel shift assay and patterned glycocalyx-mimetic surfaces successfully fabricated.

Glycosaminoglycan Mimetic Biomaterials. 2. Alkene- and Acrylate-Derivatized Glycopolymers via Cyanoxyl-Mediated Free-Radical Polymerization

Cyanoxyl (•OC⋮N)-mediated free-radical polymerization provides an effective and versatile method for engineering a diverse array of water-soluble glycopolymers with high saccharide contents and low polydispersity indexes (1.1 < Mw/Mn < 1.6). Cyanoxyl persistent radicals can be used as chain-growth moderators of the statistical copolymerization of acrylamide with either nonsulfated or sulfated N-acetyl-d-glucosamine-carrying alkene- and acrylate-derivatized unprotected glycomonomers. Moreover, monosaccharide-containing homopolymers can be prepared with some degree of control by polymerization of the acrylic glycomonomers.

Glycosaminoglycan-Mimetic Biomaterials. 1. Nonsulfated and Sulfated Glycopolymers by Cyanoxyl-Mediated Free-Radical Polymerization

Glycosaminoglycan-Mimetic Biomaterials. 1. Nonsulfated and Sulfated Glycopolymers by Cyanoxyl-Mediated Free-Radical Polymerization