Synthesis of glycopolymers bearing mannaric pendants as inhibitors on the β‐glucuronidase activity: The inhibition mechanisms of mannaric‐ and glucaric‐compounds

A new styrene derivative having D ‐mannaric moiety, N‐p‐vinylbenzyl‐D ‐mannaramic acid (VB‐D ‐ManaH, 8 ) was synthesized though the ring‐opening reaction of D ‐mannaro‐1,4:6,3‐dilactone (D ‐MDL) with p‐vinylbenzylamine. VB‐D ‐ManaH was copolymerized with acrylamide (AAm) to give novel polymers having D ‐mannaric moiety in the pendants, P(VB‐D ‐ManaH‐co‐AAm), 10 . The resulting glycomonomer and polymer ( 8 and 10 ) bearing D ‐mannaric pendants were found to inhibit the β‐glucuronidase activity, although the inhibition ability of the corresponding saccharodilactone (D ‐MDL) was known to be low. Additionally, the inhibition ability of P(VB‐D ‐ManaH‐co‐AAm), 10 , was almost the same as that of the glycopolymer having D ‐glucaric pendants, P(VB‐6‐D ‐GlcaH‐co‐AAm), 1 , which was one of the most effective inhibitors for β‐glucuronidase, reported in our previous work. Thus, 10 and 8 may be the first D ‐mannaric strong inhibitors to the β‐glucuronidase activity. The Lineweaver–Burk plot suggested that the inhibition mechanisms of 10 and 8 were more complicated than in the case of the competitive and uncompetitive inhibition of N‐p‐(vinylbenzyl)‐6‐D ‐glucaramic ( 11 ) and N‐p‐(vinylbenzyl)‐1‐D ‐glucaramic acids ( 12 ), respectively. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2032–2042, 2009     

Synthesis and properties of a well‐defined glycopolymer via living radical polymerization

A well‐defined glycopolymer was synthesized to investigate its properties. The glycopolymer was obtained with a narrow polydispersity by nitroxide‐mediated radical polymerization of styrene carrying acetylated lactose and by the subsequent deprotection. The cylindrical structure and helical conformation of the polymer were measured by circular dichroism (CD) spectra. The affinities of the polymers towards lectins depended on the degree of polymerization (DP), and the polymers with higher DP showed stronger affinity. Copyright © 2007 John Wiley & Sons, Ltd.     

High‐Density Glycosylation of Polymer Membrane Surfaces by Click Chemistry for Carbohydrate–Protein Recognition

To biologically mimic the carbohydrate–protein interactions in artificial systems, one of the challenges is to construct a glycosylated surface with a high glycosyl density to yield a notable ‘glycoside cluster effect’. A novel strategy is presented for high density glycosylation of the surface of a microporous poly(propylene) membrane (MPPM) by click chemistry. It is promising that the surface glycosyl density can be well controlled over a wide range and the maximum value is over 10 µmol · cm⁻². The recognition capability of these glycosylated MPPMs to lectins indicates the occurrence of the ‘glycoside cluster effect’ when the glycosyl density on the membrane surface exceeds 0.20 µmol · cm⁻².

     

Comparison of systematically functionalized heterogeneous and homogenous glycopolymers as toxin inhibitors

Multivalent glycosylated polymers and particles display enhanced binding affinity toward lectins compared to individual glycans. The design of glycopolymers with selectivity toward pathogen‐associated lectins (toxins) for sensing or in antiadhesion therapy is complicated due to lectins having promiscuous binding profiles and can be considered to be pattern recognition “readers,” with the capability to bind to several different glycans. Here, heterogeneous glycopolymers bearing variable densities of two different monosaccharides are synthesized by a three‐step postpolymerization modification approach, enabling systematic control over composition. It is found that heterogeneous polymers displayed increased inhibitory activity, compared to homogeneous polymers, against a RCA₁₂₀ and the cholera toxin. This demonstrates that embracing heterogeneity in glycomaterials could result in improved performance or emergent properties. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 40–47     

Glycopolymeric inhibitors of β‐glucuronidase I. Synthesis and polymerization of styrene derivatives having pendant D‐glucaric moieties

Two kinds of novel vinyl monomers having D ‐glucaric moieties leading to a new type of glycopolymeric inhibitors of β‐glucuronidase, N‐p‐vinylbenzyl‐6‐D ‐glucaramide (6 ) and potassium N‐p‐vinylbenzyl‐6‐D ‐glucaramid‐1‐ate (8 ), were synthesized by the reaction of D ‐glucaro‐6,3‐lactone (3 ) with p‐vinylbenzylamine (5 ) with no catalyst, and the subsequent treatment of the reaction mixture with acetic anhydride and potassium hydroxide aqueous solution, respectively. The radical copolymerization of 8 with acrylamide in various feed ratios at 60°C in 0.1 N potassium chloride aqueous solution gave water‐soluble copolymers (9 ) composed of a synthetic polymeric main chain and many pendant D ‐glucaric chains. The resulting glycopolymers (9 ) were found to inhibit the activity of β‐glucuronidase strongly through a model reaction with p‐nitrophenyl β‐D ‐glucuronide (10 ) in acetic buffer solution (pH 4.7). © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 303–312, 1999     

Protecting‐group‐free synthesis of glycopolymers bearing thioglycosides via one‐pot monomer synthesis from free saccharides

Polyacrylamides having pendant thioglycosides were successfully synthesized from thioglycosidic monomers that were readily prepared by one‐pot method without any protection of the hydroxy groups on the starting free saccharides. The glycomonomers were synthesized by the direct synthesis of thioglycosides using 2‐chloro‐1,3‐dimethylimidazolinium chloride and 4‐aminobenzentiol, and the following acrylamidation. They were co‐polymerized with acrylamide into glycopolymers by reversible addition‐fragmentation chain transfer polymerization using a trithiocarbonate derivative as a chain transfer agent. The gold nanoparticles and gold‐coated quartz crystal microbalance sensor immobilized with the thiol‐terminated glycopolymers exhibited high affinity for the corresponding lectins due to multivalent interaction between saccharides and protein in aqueous solution. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3513–3520     

Generation of well‐defined clickable glycopolymers from aqueous RAFT polymerization of isomaltulose‐derived acrylamides

Original carbohydrate‐based acrylamides bearing one azide group in C‐2 or C‐6 position namely, 2‐[(2‐deoxy‐2‐azido‐α‐D ‐mannopyranosyloxy)ethanamido]‐ethyl acrylamide (II) and 2‐[(6‐deoxy‐6‐azido‐α‐D ‐glucopyranosyloxy)ethanamido]‐ethyl acrylamide (III), and their azide‐free analogue, 2‐[(α‐D ‐glucopyranosyloxy)ethanamido]‐ethyl acrylamide (I), have been designed. Whereas the reversible addition fragmentation chain transfer (RAFT) process ensured the preparation of well‐defined glycopolymers from I, the polymerization of monomers II and III proved to be challenging at temperatures compatible with a thermally initiated radical process, due to the presumed concomitant 1,3‐cycloaddition reactions between the azide and the acrylamide moieties. In contrast to III, for which no polymer could be obtained under any conditions, performing the RAFT polymerization of II at 30 °C clearly favored the radical polymerization and conferred a controlled character to the process, affording well‐defined azide‐functionalized glycopolymers and block copolymers. The presence of numerous azide moieties was finally exploited to introduce carbohydrates onto the glycopolymer backbone through copper catalyzed azide‐alkyne cycloaddition. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthetic Glycopolypeptides as Potential Inhibitory Agents for Dendritic Cells and HIV‐1 Trafficking

Multivalent binding is a key for many critical biological processes and unique recognition and specificity in binding enables many of different glycans and proteins to work in a great harmony within the human body. In this study, the binding kinetics of synthetic glycopolypeptides to the dendritic cell lectin DC‐SIGN and their inhibition potential for DC‐SIGN interactions with the gp120 envelope glycoprotein of HIV‐1 (gp120) are investigated.

     

Thermo‐responsive glycopolymer chains grafted onto honeycomb structured porous films via RAFT polymerization as a thermo‐dependent switcher for lectin Concanavalin a conjugation

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