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Synthesis by high-efficiency liquid-phase (HELP) method of oligonucleotides conjugated with high-molecular weight polyethylene glycols (PEGs)
Biological Procedures Online volume 1, pages 59–69 (1998)
Abstract
The chemical modification of synthetic oligonucleotides has recently been investigated to improve their pharmacological utilization. In addition to chemical alterations of the backbone and of the heterocyclic bases, their conjugation with amphiphylic moieties, such as the polyethylene glycol has been proposed. The large scale production of these molecules as demanded for commercial purposes is hampered by the heterogeneity of the solid-phase processes and by the low reactivity of high-molecular weight PEGs in solution. A new synthetic procedure based on the recently developed liquid-phase method (HELP), has been set up to overcome these limitations.
References
Heidenreich O., Kang S.-H., Xu X., Nerenberg M. 1995. Application of Antisense to Therapeutics. Molecular Medicine Today 1, 128–133.
De Mesmaeker A., Häner R., Martin, P., Moser H. E. 1995. Antisense Oligonucleotides. Acc. Chem. Res. 28, 366–374.
Thuong, N. T., Hélène C. 1993. Sequence-Specific Recognition and Modification of Double-helical DNA by Oligonucleotides Angew. Chem., Int. Ed. Engl. 32, 666–690.
Ravikumar, V. T., Andrade M., Wyrzykievicz T., Scozzari, A., Cole, D.L. 1995. Large-scale Synthesis of Oligodeoxyribonucleotide Phosphorotioate Using Controlled-Pore Glass as Support. Nucleosides & Nucleotides 14, 1219–1222.
Bayer E., Mutter, M. 1972 Liquid Phase Synthesis of Peptides. Nature 237, 512–513.
Bonora G. M. 1995. Polyethylene Glycol. A High-Efficiency Liquid Phase (HELP) for the Large-scale Synthesis of Oligonucleotides. Appl. Biochem. Biotechnol. 54, 3–17.
Bagno A., Bicciato, S., Di Bello C., Bonora G. M. 1998. Automation of the Liquid-Phase Synthesis of Biopolymers. J. Chem. Tech. Biotechnol. 71, 77–83.
Dan Cook P. 1993. Medicinal Chemistry Strategies for Antisense Research in Antisense Research and Applications, Crooke, S.T. and Lebleu B. Eds., CRC Press Inc. Boca Raton (USA) pp.149–188.
Sanghvi TY. S. and Cook P. D. Eds. 1994. Carbohydrate Modifications in Antisense Research. ACS Symposium Series 580, Maple Press, York, PA.
Shea R. G., Marsters J. C., Bischofberger N. 1990. Synthesis, Hybridization Properties and Antiviral Acitivity of Lipid-Oligonucleotide Conjugates. Nucleic Acids Res. 18, 3777- 3783.
Boutorin A., Guskova L., Ivanova E., Kobetz N., Zarytova V., Ryte A., Yurchenko L., Vlassov V. 1989. Synthesis of Alkylating Oligonucleotide Derivatives Containing Cholesterol or Phenazinium Residues at their 3 ′-Terminus and their Interaction with DNA within Mammalian Cells. FEBS Lett. 254, 129–132.
Manoharan M., Johnson L., Bennet C. F., Vickers T. A., Ecker D. J., Cowsert L. M., Freier S. M., Cook P. D. 1994. Cholic Acid Oligonucleotide Conjugates for Antisense Application. Bioorg. Med. Chem. Lett. 4, 1053–1060.
Robles J., Maseda M., Beltran M., Concerneau M., Pedroso E., Grandas A. 1997. Synthesis and Enzymatic Stability of Phosphodiester-Linked Peptide-Oligonucleotide Hybrids. Bioconjugate Chem. 8, 785–788.
Harris J. M. Ed. 1992. Poly(ethylene Glycol) Chemistry. Biotechnical and Biomedical Applications. Plenum Press, New York.
Zalipsky S. 1995. Chemistry of Polyethylene Glycol Conjugates with Biologically Active Molecules. Adv. Drug Delivery Rev. 16, 157–182.
Efimov V. A., Pashkova I. N., Kalinkina A. L., Chakhmakhcheva O. G. 1993. Synthesis of Conjugates of Oligonucleotides with Polyethyleneglycol. Bioorg Khimi. 19, 800–804.
Jäschke A., Fürste J. P., Nordhoff E., Hillenkamp F., Cech D., Erdmann V. A. 1994. Synthesis and Properties of Oligodeoxyribonucleotides-Polyethylene Glycol Conjugates. Nucleic Acids Res. 22, 4810–4817.
Kawaguchi T., Asakana H., Tashiro Y., Juni K., Sueishi T. 1995. Stability, Specific Binding Activity, and Plasma Concentration in Mice of an Oligodeoxynucleotide Modified at 5’-Terminal with Poly(ethylene Glycol). Biol. Pharm. Bull. 18, 474–476.
Bonora G. M., Ivanova E., Zarytova V., Burcovich B., Veronese F. M. 1997. Synthesis and Characterization of High-Molecular Mass Polyethylene Glycol-Conjugated Oligonucleotides. Bioconjugate Chem. 8, 793–797.
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Bonora, G.M., Zaramella, S. & Veronese, F.M. Synthesis by high-efficiency liquid-phase (HELP) method of oligonucleotides conjugated with high-molecular weight polyethylene glycols (PEGs). Biol Proced Online 1, 59–69 (1998). https://doi.org/10.1251/bpo2
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DOI: https://doi.org/10.1251/bpo2