Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly(L-glutamic acid) backbone for inhibition of infection by influenza viruses.

Highly water-soluble glycopolymers with poly(alpha-L-glutamic acid) (PGA) backbones carrying multivalent sialyl oligosaccharides units were chemoenzymatically synthesized as polymeric inhibitors of infection by human influenza viruses. p-Aminophenyl disaccharide glycosides were coupled with gamma-carboxyl groups of PGA side chains and enzymatically converted to Neu5Acalpha2-3Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-6Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-3Galbeta1-3GalNAcalpha-, and Neu5Acalpha2-3Galbeta1-3GalNAcbeta- units, respectively, by alpha2,3- or alpha2,6-sialytransferases. The glycopolymers synthesized were used for neutralization of human influenza A and B virus infection as assessed by measurement of the degree of cytopathic inhibitory effect in virus-infected MDCK cells. Among the glycopolymers tested, alpha2,6-sialo-PGA with a high molecular weight (260 kDa) most significantly inhibited infection by an influenza A virus, strain A/Memphis/1/71 (H3N2), which predominantly binds to alpha2-6 Neu5Ac residue. The alpha2,6-sialo-PGA also inhibited infection by an influenza B virus, B/Lee/40. The binding preference of viruses to terminal sialic acids was affected by core determinants of the sugar chain, Galbeta1-4GlcNAcbeta- or Galbeta1-3GalNAcalpha/beta- units. Inhibition of infection by viruses was remarkably enhanced by increasing the molecular weight and sialic acid content of glycopolymers.

[1]  K. Nagata,et al.  Binding affinity of GM3 lactone for influenza virus , 1999, Glycoconjugate Journal.

[2]  Yasuo Suzuki,et al.  Simple synthesis of sialyllactose-carrying polystyrene and its binding with influenza virus , 1998, Glycoconjugate Journal.

[3]  Chi‐Huey Wong,et al.  Synthetic sialylphosphatidylethanolamine derivatives bind to human influenza A viruses and inhibit viral infection , 1998, Glycoconjugate Journal.

[4]  N. Bovin,et al.  Polymeric inhibitor of influenza virus attachment protects mice from experimental influenza infection. , 2002, Antiviral research.

[5]  T. Mizuochi,et al.  Carbohydrate carriers affect adhesion of H. pylori to immobilized Leb‐oligosaccharide , 2002, FEBS letters.

[6]  Chun Xing Li,et al.  Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice. , 2001, International journal of oncology.

[7]  Yoshihiro Kawaoka,et al.  Sialic Acid Species as a Determinant of the Host Range of Influenza A Viruses , 2000, Journal of Virology.

[8]  T. Murata,et al.  Chemoenzymatic synthesis of glycopolypeptides carrying alpha-Neu5Ac-(2-->3)-beta-D-Gal-(1-->3)-alpha-D-GalNAc, beta-D-Gal-(1-->3)-alpha-D-GalNAc, and related compounds and analysis of their specific interactions with lectins. , 2000, Archives of biochemistry and biophysics.

[9]  B. Jin,et al.  Synthesis of a polymeric 4-N-linked sialoside which inhibits influenza virus hemagglutinin. , 2000, Bioorganic & medicinal chemistry letters.

[10]  S. Nishimura,et al.  Synthesis and anti-influenza virus activity of novel glycopolymers having triantennary oligosaccharide branches , 2000 .

[11]  M. Hashida,et al.  Development of a hepatocyte-specific prostaglandin E(1) polymeric prodrug and its potential for preventing carbon tetrachloride-induced fulminant hepatitis in mice. , 1999, The Journal of pharmacology and experimental therapeutics.

[12]  J. Baker,et al.  Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers. , 1999, Bioconjugate chemistry.

[13]  H. Kawagishi,et al.  Analysis of specific interactions of synthetic glycopolypeptides carrying N-acetyllactosamine and related compounds with lectins. , 1998, Carbohydrate research.

[14]  Chi‐Huey Wong,et al.  A Lysoganglioside/Poly-L-glutamic Acid Conjugate as a Picomolar Inhibitor of Influenza Hemagglutinin. , 1998, Angewandte Chemie.

[15]  Chun Xing Li,et al.  Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. , 1998, Cancer research.

[16]  S. Morey,et al.  Development and Characterization of Monoclonal Antibody to T-Antigen: (Galβl—3GalNAc-α-O) , 1998 .

[17]  M. Hashida,et al.  Synthesis and biodistribution study of liver-specific prostaglandin E1 polymeric conjugate , 1997 .

[18]  G. Whitesides,et al.  Generation and in Situ Evaluation of Libraries of Poly(acrylic acid) Presenting Sialosides as Side Chains as Polyvalent Inhibitors of Influenza-Mediated Hemagglutination , 1997 .

[19]  Y. Kawaoka,et al.  Sulphatide binds to human and animal influenza A viruses, and inhibits the viral infection. , 1996, The Biochemical journal.

[20]  Y. Ikada,et al.  A new biological glue from gelatin and poly (L-glutamic acid). , 1996, Journal of biomedical materials research.

[21]  G. Whitesides,et al.  Polyacrylamides Bearing Pendant α-Sialoside Groups Strongly Inhibit Agglutination of Erythrocytes by Influenza Virus: The Strong Inhibition Reflects Enhanced Binding through Cooperative Polyvalent Interactions , 1996 .

[22]  G M Whitesides,et al.  Effective inhibitors of hemagglutination by influenza virus synthesized from polymers having active ester groups. Insight into mechanism of inhibition. , 1995, Journal of medicinal chemistry.

[23]  H. Klenk,et al.  Suppression of influenza virus infection by an N-thioacetylneuraminic acid acrylamide copolymer resistant to neuraminidase. , 1995, Virology.

[24]  S. Asawa,et al.  Use of lactate dehydrogenase to evaluate the anti-viral activity against influenza A virus. , 1995, Journal of virological methods.

[25]  R. Gurny,et al.  In vitro and in vivo evaluation of progesterone implants based on new biodegradable poly(glutamic and glutamate esters) copolymers. , 1995, Journal of biomaterials science. Polymer edition.

[26]  D. Tudor,et al.  Local Treatment of Pressure Sores in the Elderly: Amino Acid Copolymer Membrane Versus Hydrocolloid Dressing , 1994, Journal of the American Geriatrics Society.

[27]  G M Whitesides,et al.  Polyacrylamides bearing pendant alpha-sialoside groups strongly inhibit agglutination of erythrocytes by influenza A virus: multivalency and steric stabilization of particulate biological systems. , 1994, Journal of medicinal chemistry.

[28]  R. Webster,et al.  Sialoglycoproteins that bind influenza A virus and resist viral neuraminidase in different animal sera. , 1994, The Journal of general virology.

[29]  W. Watanabe,et al.  MTT colorimetric assay system for the screening of anti-orthomyxo- and anti-paramyxoviral agents. , 1994, Journal of virological methods.

[30]  M. Kiso,et al.  Specificity of sialyl-sugar chain mediated recognition by the hemagglutinin of human influenza B virus isolates. , 1994, Journal of biochemistry.

[31]  E. De Clercq,et al.  In vitro and in vivo inhibition of ortho- and paramyxovirus infections by a new class of sulfonic acid polymers interacting with virus-cell binding and/or fusion , 1994, Antimicrobial Agents and Chemotherapy.

[32]  T. Akaike,et al.  [21] Synthesis of poly(N-acetyl-β-lactosaminide-carrying acrylamide): Chemical-enzymatic hybrid process , 1994 .

[33]  Y. Suzuki,et al.  Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains. , 1994, Progress in lipid research.

[34]  A. Golbraikh,et al.  Probing of the receptor-binding sites of the H1 and H3 influenza A and influenza B virus hemagglutinins by synthetic and natural sialosides. , 1993, Virology.

[35]  Y. Suzuki.  [Variation of influenza viruses and their recognition of the receptor sialo-sugar chains]. , 1993, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[36]  M. Kashem,et al.  Determination of the specificities of rat liver Gal(beta 1-4)GlcNAc alpha 2,6-sialyltransferase and Gal(beta 1-3/4)GlcNAc alpha 2,3-sialyltransferase using synthetic modified acceptors. , 1993, The Journal of biological chemistry.

[37]  H. Ohi,et al.  A convenient synthesis of β-d-galactosyl disaccharide derivatives using the β-d-galactosidase from Bacillus circulans , 1993 .

[38]  G. Whitesides,et al.  Neuraminidase-resistant hemagglutination inhibitors: acrylamide copolymers containing a C-glycoside of N-acetylneuraminic acid. , 1993, Journal of medicinal chemistry.

[39]  J. Feijen,et al.  BIOLOGICAL PROPERTIES OF ADRIAMYCIN BOUND TO BIODEGRADABLE POLYMERIC CARRIERS , 1993 .

[40]  A. Jackman,et al.  The role of the reduced-folate carrier and metabolism to intracellular polyglutamates for the activity of ICI D1694. , 1993, Advances in experimental medicine and biology.

[41]  T. Ito,et al.  Structural determination of gangliosides that bind to influenza A, B, and C viruses by an improved binding assay: strain-specific receptor epitopes in sialo-sugar chains. , 1992, Virology.

[42]  J. Knowles,et al.  Monovalent sialosides that bind tightly to influenza A virus. , 1991, Journal of medicinal chemistry.

[43]  A. Gamian,et al.  Inhibition of influenza A virus hemagglutinin and induction of interferon by synthetic sialylated glycoconjugates. , 1991, Canadian journal of microbiology.

[44]  Sera,et al.  Distinct glycoprotein inhibitors of influenza A virus in different animal sera , 1991, Journal of virology.

[45]  G. Whitesides,et al.  Polyacrylamides bearing pendant .alpha.-sialoside groups strongly inhibit agglutination of erythrocytes by influenza virus , 1991 .

[46]  G M Whitesides,et al.  Hemagglutinins from two influenza virus variants bind to sialic acid derivatives with millimolar dissociation constants: a 500-MHz proton nuclear magnetic resonance study. , 1989, Biochemistry.

[47]  J. Paulson,et al.  4-O-acetyl-N-acetylneuraminic acid in the N-linked carbohydrate structures of equine and guinea pig alpha 2-macroglobulins, potent inhibitors of influenza virus infection. , 1989, The Journal of biological chemistry.

[48]  J. Paulson,et al.  Basis for the potent inhibition of influenza virus infection by equine and guinea pig alpha 2-macroglobulin. , 1989, The Journal of biological chemistry.

[49]  A. Edge,et al.  Presence of an O-glycosidically linked hexasaccharide in fetuin. , 1987, The Journal of biological chemistry.

[50]  J. Paulson,et al.  Recognition of monovalent sialosides by influenza virus H3 hemagglutinin. , 1987, Virology.

[51]  J. Paulson,et al.  Combined chemical and enzymatic synthesis of sialyloligosaccharides and characterization by 500-MHz and proton and carbon-13 NMR spectroscopy , 1986 .

[52]  Vasilov Rg,et al.  Artificial peptide and carbohydrate antigens. Immobilization of haptens and adjuvant (MDP) on polyacrylamide , 1986 .

[53]  J. Paulson,et al.  Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants. , 1983, Virology.

[54]  J. Paulson,et al.  Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. , 1983, Virology.

[55]  I. Pardoe,et al.  A sialoglycopeptide from human erythrocytes with receptor-like properties for encephalomyocarditis and influenza viruses. , 1983, The Journal of general virology.

[56]  T. Suzuki,et al.  Isolation and characterization of receptor sialoglycoprotein for hemagglutinating virus of Japan (Sendai virus) from bovine erythrocyte membrane. , 1983, Journal of biochemistry.

[57]  J. Paulson,et al.  Purification of a Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase and a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase to homogeneity from rat liver. , 1982, The Journal of biological chemistry.

[58]  J U Baenziger,et al.  Structure of the complex oligosaccharides of fetuin. , 1979, The Journal of biological chemistry.

[59]  T. Boat,et al.  Effect of blood group determinants on binding of human salivary mucous glycoproteins to influenza virus. , 1978, Biochimica et biophysica acta.

[60]  P. Spencer,et al.  Nervous system degeneration produced by acrylamide monomer. , 1975, Environmental health perspectives.