Abstract
A protocol for the rapid, automated synthesis of oligospermine–oligonucleotide sequences is described. To this end, a protected spermine phosphoramidite derivative was synthesized in six steps from spermine and used as the fifth synthon in an oligonucleotide synthesizer. Parameters were optimized to reach greater than 95% coupling yields. Cationic oligonucleotides show enhanced hybridization and strand invasion properties, and hence are an alternative to conventional oligonucleotides for molecular biology, diagnostic and potential therapeutic applications. A multi-gram-scale synthesis of the spermine phosphoramidite allowing several hundred coupling steps takes 2–3 weeks. Oligonucleotide synthesis and purification takes approximately 3 d.
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Dr Behr is a minor shareholder of a company that licensed this technology.
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Voirin, E., Behr, JP. & Kotera, M. Versatile synthesis of oligodeoxyribonucleotide–oligospermine conjugates. Nat Protoc 2, 1360–1367 (2007). https://doi.org/10.1038/nprot.2007.177
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DOI: https://doi.org/10.1038/nprot.2007.177
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