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Abstract

Glycoconjugate polystyrenes bearing sialyllactose moieties were prepared via a simple method from a mixture of alpha2-6 and a2-3 linked sialyllactose isomers of bovine milk origin. The reducing end of sialyllactose was converted to an amino function with ammonium hydrogen carbonate and then coupled with p-vinylbenzoyl chloride. The resulting styrene derivative substituted with sialyllactose via an amide linkage was polymerized with ammonium peroxodisulfate and N,N,N',N-tetramethylethylenediamine in water at 30 degrees C. The interaction of the glycopolymer with influenza A and B viruses was investigated by three different methods. The glycopolymer inhibited the hemagglutination of influenza A virus (PR/8/34) and its activity was 10(3) times higher than that of the oligosaccharide itself. The cytopathic effect of virus-infected MDCK (Madine-Darby canine kidney) cells was inhibited by the glycopolymer. The homopolymer showed 10(2) times higher inhibitory activity than naturally-occurring fetuin. It was also found that various viruses could be trapped by the glycopolymer adsorbed on a polystyrene surface. The inhibitory and trapping activities of the glycopolymers were correlated with the sialyl linkage specificities of the virus strains.

Sialobiology of Influenza: Molecular Mechanism of Host Range Variation of Influenza Viruses

“…The shape of the glycopeptide protein scaforld, which is determined by the amino acid sequences employed, is also found to be significant in determining the inhibitory activity. 87) We also developed glycopolymers containing multivalent sialyloligosaccharides (Neu5Aca2-3Galb1-4GlcNAcb1-, Neu5Aca2-6Galb1-4GlcNAcb1-, Neu5Aca2-3Galb1-3Gal-NAca1-, Neu5Aca2-3Galb1-3GalNAcb1-) with a poly (Lglutamic acid) backbone, 88) triantennary oligosaccharide branches (Neu5Aca2-3Galb1-4GlcNAcb1-, Neu5Aca2-6Galb1-4GlcNAcb1-) with a polyacrylamide backbone, 89) and sialyllactose (Neu5Aca2-3Galb1-4Glcb1-; Neu5Aca2-6Galb1-4Glcb1-) with a polystyrene backbone 90) that inhibit the receptor binding function of the hemagglutinin of influenza viruses. The glycopolymer inhibited the hemagglutination of influenza A virus, and its activity level was 10 3 -times higher than that of the oligosaccharide itself, indicating that clustering of the sugar chain in the polymer backbone may be important for inhibitory activity of the viral hemagglutinin.…”

“…The glycopolymer inhibited the hemagglutination of influenza A virus, and its activity level was 10 3 -times higher than that of the oligosaccharide itself, indicating that clustering of the sugar chain in the polymer backbone may be important for inhibitory activity of the viral hemagglutinin. 90) A macrocyclic sialic acid cluster inhibits human influenza virus (H1 and H3 subtypes) hemagglutination. 91) A lyso GM3 ganglioside to which hydrophobic molecule (BODYPY) was linked/poly-L-glutamic acid conjugate was designated.…”

Inhibition of Influenza Virus Activity by Multivalent Glycoarchitectures with Matched Sizes

“…[13,18] The vast majority of amorphous linear polymers used were either copolymers of acrylamide esters used by Roy, [19] Whitesides, [20] Bovin, [21] Matrosovich, [5,22] and Watson; [23] or copolymers of acrylic acid esters, [20c, 24] polystyrene, [25] and others. [26] Here, multivalency offers some major advantages.…”

Synthetic sialic-acid-containing polyvalent antiviral inhibitors

“…• The molecular weight, charges, bulky and hydrophobic groups of the glycopolymers • Steric stabilization of the glycopolymers • The distribution of sialic acid chain into glycopolymers • The degree of freedom of the sialoside moiety in the glycopolymer The backbones that have been used so far including poly(acrylamide) (Spaltenstein and Whitesides et al, 1991;Roy et al, 1992;Lees et al, 1994;Sigal et al, 1996;Choi et al, 1996;Bovin, 1998), poly(acrylic acid) (Choi et al, 1997;Tuzikov et al, 2000;Barclay et al, 2007), chitosan (Sashiwa et al, 2000a;Makimura et al, 2006), poly(styrene) (Tsuchida et al, 1998), and poly(glutamic acid) (Kamitakahara et al, 1998;Totani et al, 2003;Ogata et al, 2007).…”