title: Improved synthesis of oligonucleotides with an allylic backbone. Oligonucleotides containing acyclic, achiral nucleoside analogues: N-1 or N-9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases.
abstract: An improved phosphoramidite method is described to prepare oligonucleotides modified with the acyclic, achiral monomers 1. Examination of dimers, prepared on solid support or in solution, showed that phosphortriester dimers containing the allylic unit 1 were unstable towards bases, whereas phosphordiester dimers were stable. Phosphordiester dimers were obtained by replacing cyanoethyl phosphoramidites 2 with phosphoramidites 3, which gave phosphordiesters directly upon oxidation. The phosphordiester dimers were found to be stable towards capping and oxidation, but were somewhat labile towards acids. By reducing the contact time to acids during detritylation it was possible to prepare oligonucleotides containing 4 or 8 modified A, G or T units. The modified oligonucleotides hybridized to complementary DNA and RNA, although with reduced affinity (DeltaT(m) per modification -1 to -5 degrees C).
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark.
authors.forename: Britta M
authors.initials: BM
authors.lastname: Dahl
authors.forename: Ulla
authors.initials: U
authors.lastname: Henriksen
authors.forename: Otto
authors.initials: O
authors.lastname: Dahl
mesh_terms: D000577:Amides; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification; D010755:Organophosphates / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry*; D063088:Phosphoramides; D010756:Phosphoric Acids; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000577:Amides; D007202:Indicators and Reagents; D009705:Nucleosides; D009841:Oligonucleotides; D010755:Organophosphates; D063065:Organophosphonates; D063088:Phosphoramides; D010756:Phosphoric Acids; C005438:phosphoramide