Abstract
Oligonucleotide–peptide conjugates have attracted considerable interest especially for biomedical uses. In the first part of this chapter, we describe protocols for the stepwise synthesis of oligonucleotides carrying peptide sequences at the 3′-end on a single support. The resulting oligonucleotide–peptide conjugates may be used as exogenous effectors for the specific control of gene expression. In the second part of this chapter, detailed postsynthetic conjugation protocols to introduce peptide sequences into oligonucleotide sequences are also presented.
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References
Eritja, R., Pons, A., Escarceller, M., Giralt, E., and Albericio, F. (1991) Synthesis of defined peptide-oligonucleotide hybrids containing a nuclear transport signal sequence. Tetrahedron 47, 4113–4120.
Soukchareun, S., Tregear, G.W., and Haralambidis, J. (1995) Preparation and characterization of antisense oligonucleotide-peptide hybrids containing viral fusion peptides. Bioconjug. Chem. 6, 43–53.
de la Torre, B.G., Aviñó, A., Tarrasón, G., Piulats, J., Albericio, F., and Eritja, R. (1994) Stepwise solid-phase synthesis of oligonucleotide-peptide hybrids. Tetrahedron Lett. 35, 2733–2736.
de la Torre, B.G., Albericio, F., Saison-Behmoaras, E., Bachi, A., Eritja, R. (1999) Synthesis and binding properties of oligonucleotides carrying nuclear localization sequences. Bioconjug. Chem. 10, 1005–1012.
Tung, C.H., and Stein, S. (2000) Preparation and applications of peptide-oligonucleotide conjugates. Bioconjug. Chem. 11, 605–618.
Eritja, R. (2000) Synthesis of oligonucleotide-peptide conjugates and nucleopeptides. Solid-Phase Synthesis. A practical guide. (S. Kates, F. Albericio Eds) Marcel Dekker, New York, pp529-548.
Grandas, A., Marchán, V., Debéthune, L., and Pedroso, E. (2004) Stepwise solid-phase synthesis of nucleopeptides. Current Protocols in Nucleic Acid Chemistry, John Willey & Sons, NY, Chapt. 4.22.1–4.22.54.
Röglin, L., Seitz, O. (2008) Controlling the activity of peptides and proteins with smart nucleic acid-protein hybrids. Org. Biomol. Chem. 6, 3881–3887.
Venkatesan, N., and Kim, B.H. (2006) Peptide conjugates of oligonucleotides: synthesis and applications. Chem. Rev. 106, 3712–3761.
Gait, M.J. (2003) Peptide-mediated cellular delivery of antisense oligonucleotides and their analogues. Cell Mol. Life Sci. 60, 844–853.
Brumcot, D., Manoharan, M., Koteliansky, V., and Sah, D.W. (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol. 2, 711–719.
Aviñó, A., Ocampo, S. M., Caminal, C., Perales, J.C., and Eritja, R. (2009) Stepwise synthesis of RNA conjugates carrying peptide sequences for RNA interference studies. Mol. Divers. 13, 287–293.
Gottschling, D., Seliger, H., Tarrasón, G., Piulats, J., Eritja, R (1998) Synthesis of oligodeoxynucleotides containing N4-mercaptoethylcytosine and their use in the preparation of oligonucleotide-peptide conjugates carrying c-myc tag sequence. Bioconjug. Chem. 9, 831–837.
Frieden, M., Aviñó, A., Tarrasón, G., Escorihuela, M., Piulats, J., Eritja, R. (2004) Synthesis of oligonucleotide-peptide conjugates carrying the c-myc peptide epitope as recognition system. Chem. Biodivers. 1, 930–938.
Merkoçi, A., Aldavert, M., Tarrasón, G., Eritja, R., Alegret, S. (2005) Toward an ICPMS-Linked DNA assay based on gold nanoparticles immunoconnected through peptide sequences. Anal. Chem. 77, 6500–6503.
Portela, C., Albericio, F., Eritja, R., Castedo, L., Mascareñas, J.L. (2007) Ds-Oligonu-cleotide-peptide conjugates featuring peptides from the leucine zipper region of fos as switchable receptors for the oncoprotein Jun. ChemBioChem 8, 1110–1114.
Debethune, L., Marchan, V., Fabregas, G., Pedroso, E. Grandas, A. (2002) Towards nucleopeptides containing any trifunctional amino acid (II) Tetrahedron 58, 6955–6978.
Zaramella, S.; Yeheskiely, E.; Strömberg, R. (2004) A method for solid-phase synthesis of oligonucleotide 5’-peptide-conjugates using acid-labile alpha-amino protections. J. Am. Chem. Soc. 126, 14029–14035.
Ocampo, S. M., Albericio, F., Fernández, I., Vilaseca, M., Eritja, R. (2005) A straightforward synthesis of 5’-peptide oligonucleotide conjugates using Nα-Fmoc-protected amino acids. Org. Lett. 7, 4349–4352.
Acknowledgments
This work is supported by the Spanish Ministry of Education (BFU2007-63287/BMC), Generalitat de Catalunya (2009/SGR/238), Instituto de Salud Carlos III (CIBER-BNN), and European Communities (DYNAMO contract 028669 (NEST), FUNMOL NMP4-SL-2009-213382).
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Aviñó, A., Grijalvo, S., Pérez-Rentero, S., Garibotti, A., Terrazas, M., Eritja, R. (2011). Synthesis of Oligonucleotide–Peptide Conjugates for Biomedical and Technological Applications. In: Mark, S. (eds) Bioconjugation Protocols. Methods in Molecular Biology, vol 751. Humana Press. https://doi.org/10.1007/978-1-61779-151-2_14
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DOI: https://doi.org/10.1007/978-1-61779-151-2_14
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