Facile Synthesis of Chain-End Functionalized Glycopolymers for Site-Specific Bioconjugation (original) (raw)

Abstract

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 R and ω chain ends. In the process, the capacity to label glycopolymers or otherwise conjugate them to proteins or other molecules is greatly enhanced.

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.

References (42)

  1. Lee, Y., and Lee, R. T. (1995) Carbohydrate-protein interac- tions: basis of glycobiology. Acc. Chem. Res. 28, 321.
  2. Strong, L. E., and Kiessling, L. L. (1999) A general synthetic route to defined, biologically active multivalent arrays. J. Am. Chem. Soc. 121, 6193.
  3. Lundquist, J. J., and Toone, E. J. (2002) The cluster glycoside effect. Chem. Rev. 102, 555.
  4. D'Agosto, F., Charreyye, M. T., Pichot, C., and Mandrand, B. (2002) Polymer of controlled chain length carrying hydro- philic galactose moieties for immobilization of DNA probes. Macromol. Chem. Phys. 203, 146.
  5. D'Agosto, F., Charreyye, M. T., Delolme, F., Dessalces, G., Cramail, H., Deffieux, A., and Pichot, C. (2002) Kinetic study of the "living" cationic polymerization of a galactose carrying vinyl ether. MALDI-TOF MS analysis of the resulting gly- copolymers. Macromolecules 35, 7911.
  6. Yamada, K., Minoda, M., and Miyamoto, T. (1999) Con- trolled synthesis of amphiphilic block copolymers with pen- dant N-acetyl-D-glucosamine residues by living cationic polymerization and their Interaction with WGA lectin. Macro- molecules 32, 3553.
  7. Yamada, K., Minoda, M., and Miyamoto, T. (1997) Con- trolled synthesis of glycopolymers with pendant D-glu- cosamine residues by living cationic polymerization. J. Polym. Sci., Part A: Polym. Chem. 35, 751.
  8. Tsutsumiuchi, K., Aoi, K., and Okada, M. (1997) Synthesis of polyoxazoline-(Glyco)peptide block copolymers by ring- opening polymerization of (Sugar-Substituted) R-amino acid N-carboxyanhydrides with polyoxazoline macroinitiators. Macromolecules 30, 4013.
  9. Aoi, K., Tsutsumiuchi, K., and Okada, M. (1994) Glycopep- tide synthesis by an alpha-amino acid N-carboxyanhydride (NCA) method: ring-opening polymerization of a sugar- substituted NCA. Macromolecules 27, 875.
  10. Nomura, K., and Schrock, R. R. (1996) Preparation of "sugar-coated" homopolymers and multiblock ROMP copoly- mers. Macromolecules 29, 540.
  11. Fraser, C., and Grubbs, R. U. (1995) Synthesis of glyco- polymers of controlled molecular weight by ring-opening metathesis polymerization using well-defined functional group tolerant ruthenium carbene catalysts. Macromolecules 28, 7248.
  12. Gotz, H., Horth, E., Schiller, S. M., Frank, C. W., Knoll, W., and Hawker, C. J. (2002) Synthesis of lipo-glycopolymer amphiphiles by nitroxide-mediated living free-radical polym- erization. J. Polym. Sci., Part A: Polym. Chem. 40, 3379.
  13. Chen, Y. M., and Wulff, G. (2001) Synthesis of poly(styryl sugar)s by TEMPO mediated free radical polymerization. Macromol. Chem. Phys. 202, 3426.
  14. Chen, Y. M., and Wulff, G. (2001) Amphiphilic block copolymers with pendent sugar as hydrophilic segments and their surface properties. Macromol. Chem. Phys. 202, 3273.
  15. Narumi, A., Matsuda, T., Kaga, H.; Satoh, T., and Kakuchi, T. (2001) Glycoconjugated polymer II. Synthesis of polystyrene- block-poly(4-vinylbenzyl glucoside) and polystyrene-block- poly(4-vinylbenzyl maltohexaoside) via 2,2,6,6-tetramethylpi- peridine-1-oxyl-mediated living radical polymerization. Polym. J. 33, 939.
  16. Ohno, K., Tsujii, Y., Miyamoto, T., Fukuda, T., Goto, M., Kobayashi, K., and Akaike, T. (1998) Synthesis of a well- defined glycopolymer by nitroxide-controlled free radical polymerization. Macromolecules 31, 1064.
  17. Chen, Y. M., and Wulff, G. (2002) ABA and star am- phiphilic block copolymers composed of polymethacrylate bearing a galactose fragment and poly( -caprolactone). Mac- romol. Rapid Commun. 23, 59.
  18. Li, Z. C., Liang, Y. Z., Chen, G. Q., and Li, F. M. (2000) Synthesis of amphiphilic block copolymers with well-defined glycopolymer segment by atom transfer radical polymeriza- tion. Macromol. Rapid Commun. 21, 375.
  19. Haddleton, D. M., and Ohno, K. (2000) Well-defined oligosaccharide-terminated polymers from living radical po- lymerization. Biomacromolecules 1, 152.
  20. Ohno, K., Tsujii, Y., and Fukuda, T. (1998) Synthesis of a well-defined glycopolymer by atom transfer radical polymer- ization. J. Polym. Sci., Part A: Polym. Chem. 36, 2473.
  21. Okada, M. (2001) Molecular design and syntheses of glycopolymers. Prog. Polym. Sci. 26, 67.
  22. Roy, R., Tropper, F. D., and Romanowska, A. (1992) Custom-designed glycopolymer syntheses by terpolymeriza- tions. J. Chem. Soc., Chem. Commun. 1611.
  23. Thoma, G., Patton, J. T., Magnani, J. L., Ernst, B., O ¨hrlein, R., and Duthaler, R. O. (1999) Versatile functionalization of polylysine: synthesis, characterization, and use of neoglyco- conjugates. J. Am. Chem. Soc. 121, 5919.
  24. Gorden, E. J., Gestwicki, J. E., Strong, L. E. and Kiessling, L. L. (2000) Synthesis of end-labeled multivalent ligands for exploring cell-surface-receptor-ligand interactions. Chem. Biol. 7, 9.
  25. Gestwicki, J. E., Cairo, C. W., Mann, D. A., and Kiessling, L. L. (2002) Selective immobilization of multivalent ligands for surface plasmon resonance and fluorescence microscopy. Anal. Biochem. 305, 149.
  26. Rye, P. D., and Bovin, N. V. (1997) Selection of carbohydrate- binding cell phenotypes using oligosaccharide-coated mag- netic particles. Glycobiology 7, 179.
  27. Bundy, J. L., and Fenselau, C. (2001) Lectin and carbo- hydrate affinity capture surfaces for mass spectrometric analysis of microorganisms. Anal. Chem. 73, 751.
  28. Yoshizumi, A., Kanayama, N., Maehara, Y., Ide, M., and Kitano, H. (1999) Self-assembled monolayer of sugar-carrying polymer chain: Sugar balls from 2-methacryloyloxyethyl D-glucopyranoside. Langmuir 15, 482.
  29. Sun, X. L., Faucher, K. M., Houston, M., Grande, D., and Chaikof, E. L. (2002) Design and synthesis of biotin chain- terminated glycopolymers for surface glycoengineering. J. Am. Chem. Soc. 124, 7258.
  30. Grande, D., Baskaran, S., Basakaran, C., Gnanou, Y., and Chaikof, E. L. (2000) Glycosaminoglycan-mimetic biomate- rials. 1. Nonsulfated and sulfated glycopolymers by cyanoxyl- mediated free-radical polymerization. Macromolecules 33, 1123.
  31. Sun X. L., Grande, D., Baskaran, S., and Chaikof, E. L. (2002) Glycosaminoglycan mimetic biomaterials. 4. Synthesis of sulfated lactose-based glycopolymers that exhibit antico- agulant activity. Biomacromolecules 3, 1065.
  32. Sigal, G. B., Mammen, M., Dahmann, G., and Whitesides, G. M. (1996) Polyacrylamides bearing pendant R-sialoside groups strongly inhibit agglutination of erythrocytes by influenza virus: The strong inhibition reflects enhanced binding through cooperative polyvalent interactions. J. Am. Chem. Soc. 118, 3789.
  33. Scheme 3. Conversion of Terminal Glycopolymer Cyanate Group (OCN) to a Hydroxyl Moiety
  34. Bovin, N. V. (1998) Polyacrylamide-based glycoconjugates as tools in glycobiology. Glycoconjugate J. 15, 431.
  35. March, J. (1985) Aromatic electrophilic substitution. Adv. Org. Chem. 447-511.
  36. Weber, P. C., Ohlendore, D. H., Wendoloski, J. J., and Salemme, F. R. (1989) Structural origins of high-affinity biotin binding to streptavidin. Science 243, 85.
  37. Hanink, J. M., Cornelissen, J. L. M., Farrera, J. A., Foubert, P. De Schryver, F. C., Sommerdijk, N. A. J. M., and Nolte, R. J. M. (2001) Protein-polymer hybrid amphiphiles. Angew. Chem, Int. Ed. 40, 4732.
  38. Weber, P. C., Wendoloski, J. J., Pantoliano, M. W., and Salemme, F. R. (1992) Crystallographic and thermodynamic comparison of natural and synthetic ligands bound to strepta- vidin. J. Am. Chem. Soc. 114, 3197.
  39. Axen, R., Porath, J., and Ernback, S. (1967) Chemical coupling of peptides and proteins to polysaccharides by means of cyanogen bromide. Nature 214, 1302.
  40. Wilchek, M., and Miron, T. (1999) Thirty years of affinity chromatography. React. Funct. Polym. 41, 263.
  41. Lees, A., Nelson, B. L., and Mond, J. J. (1996) Activation of soluble polysaccharides with 1-cyano-4-dimethylaminopy- ridiniumtetrafluoroborate for use in protein-polysaccharide conjugate vaccines and immunological reagents. Vaccine 14, 190.
  42. Kohn, J., and Wilchek, M. (1978) A colorimetric method for monitoring activation of sepharose by cyanogen bromide. Biochem. Biophys. Res. Commun. 84, 7. BC0499275