Versatile synthesis of oligodeoxyribonucleotide-oligospermine conjugates.
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.
Voirin
Emilie
E
Polyplus-transfection SA, Bioparc, Boulevard S. Brandt, BP90018, 67401 Illkirch, France.
Behr
Jean-Paul
JP
Kotera
Mitsuharu
M
D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D013096:Spermine / Q000737:chemistry*
D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D013096:Spermine