Synthesis and Aggregation Behavior of Temperature- and pH-Responsive Glycopolymers as Sugar-Displaying Conjugates

Abstract

Stimuli-responsive polymers have attracted significant interest in the fields of advanced materials and biomaterials. Herein, temperature- and pH-responsive glycopolymers, which are composed of N-isopropylacrylamide, methacrylic acid, and an acrylamide derivative bearing a lactose moiety, were synthesized via radical copolymerization. The series of resulting glycopolymers had different degrees of substitution of the lactose moieties, were responsive to temperatures between 26.6 °C and 47.6 °C, and formed aggregates above the lower critical solution temperature limit in mild acidic aqueous media (pH 4–6). The temperature-responsive behavior was dependent on the prevailing pH conditions, as no aggregation was observed in neutral and basic aqueous media (pH > 7). The aggregates had saccharide moieties on the surface in aqueous media. The number of saccharide moieties on the surface depended on the saccharide-containing unit ratio in the glycopolymer. The ratio was determined via enzymatic hydrolysis of the lactose moieties using β-galactosidase and the subsequent detection of the released galactose.

Glycopolymers based on carbohydrate or vinyl backbones and their biomedical applications

“…41 It was found that PNiPAm was hydrophilic below the lower critical solution temperature (LCST) but became hydrophobic above the LCST. 41,86 Similarly, a polyphosphonium consisting of a pendant mannose moiety with alkyl trithiocarbonate and carboxylic acid end groups was reported by Gillies and Ragogna et al 87 Besides, Gibson et al designed telechelic homopolymers with a pentafluorophenyl ester at the one end and a thiol at the other. 88 Then, mannose and galactose could be introduced by the reaction of the pentafluorophenol end group with 2-deoxy-2-amino mannose and 2-deoxy-2-amino galactose, respectively, while Au nanoparticles (NPs) can be immobilized by another thiol end group.…”

Hierarchy of Complex Glycomacromolecules: From Controlled Topologies to Biomedical Applications

“…Another type of stimuli-responsive behavior is light-responsiveness, and Stenzel et al have reported block copolymers of azobenzene-containing blocks and galactose-functionalized blocks . Multistimuli-responsive glycomacromolecules have also been reported, , although in a random copolymerization manner, and these studies indicate the potential of preparing well-defined, multiresponsive block copolymers of glycopolymers. These studies of incorporating stimuli-responsive properties with glycopolymers show that manufacturing of smart polymer systems with desired stimuli-responsive and cell recognition properties is possible, and this approach could contribute to the development of novel smart biomaterials or controlled drug-delivery systems.…”

Recent Advances in Polymers Bearing Activated Esters for the Synthesis of Glycopolymers by Postpolymerization Modification

“…Huisgen cycloaddition has been employed to synthesize numerous glycomonomers and glycopolymers with the Haddleton, Gibson, Becer, and Miura groups, and many others [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. The authors reported the synthesis of glycopolymers by Huisgen cycloaddition in the postpolymerization modification using glycosyl azides, which were directly synthesized from unprotected saccharides using a water-soluble dehydration condensation agent, 2-chloro-1,3-dimethylimidazolinium chloride in water [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Many reports exist on the investigation of the binding affinity of glycopolymers synthesized by Huisgen cycloaddition and other methods used against influenza viruses and their proteins [ 45 , 56 , 57 , 62 , 63 ].…”

“…Click chemistry, such as azide-alkyne cycl (Huisgen cycloaddition) [31][32][33] and thiol-ene reactions [34][35][36][37], is frequently in postpolymerization modification. This is because, in most cases, click chem tions do not produce byproducts, and they enable the facile linking of molecule cycloaddition has been employed to synthesize numerous glycomonomers and ymers with the Haddleton, Gibson, Becer, and Miura groups, and many othe The authors reported the synthesis of glycopolymers by Huisgen cycloaddi postpolymerization modification using glycosyl azides, which were directly s from unprotected saccharides using a water-soluble dehydration condensatio chloro-1,3-dimethylimidazolinium chloride in water [55][56][57][58][59][60][61]. Many reports e investigation of the binding affinity of glycopolymers synthesized by Huisgen tion and other methods used against influenza viruses and their proteins [45,5 Various other reactions have been used, such as those of maleimide and thiol; and amine; isothiocyanate and thiol; epoxide and alcohol; azlactone and amin vated esters and amine.…”