title: N-Branched acyclic nucleoside phosphonates as monomers for the synthesis of modified oligonucleotides.
abstract: Protected N-branched nucleoside phosphonates containing adenine and thymine bases were prepared as the monomers for the introduction of aza-acyclic nucleotide units into modified oligonucleotides. The phosphotriester and phosphoramidite methods were used for the incorporation of modified and natural units, respectively. The solid phase synthesis of a series of nonamers containing one central modified unit was successfully performed in both 3'→5' and 5'→3' directions. Hybridization properties of the prepared oligoribonucleotides and oligodeoxyribonucleotides were evaluated. The measurement of thermal characteristics of the complexes of modified nonamers with the complementary strand revealed a considerable destabilizing effect of the introduced units. We also examined the substrate/inhibitory properties of aza-acyclic nucleoside phosphono-diphosphate derivatives (analogues of nucleoside triphosphates) but neither inhibition of human and bacterial DNA polymerases nor polymerase-mediated incorporation of these triphosphate analogues into short DNA was observed.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic. hockova@uochb.cas.cz Ivan.Rosenberg@uochb.cas.cz.
authors.forename: Dana
authors.initials: D
authors.lastname: Hocková
authors.forename: Šárka
authors.initials: Š
authors.lastname: Rosenbergová
authors.forename: Petra
authors.initials: P
authors.lastname: Ménová
authors.forename: Ondřej
authors.initials: O
authors.lastname: Páv
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.forename: Pavel
authors.initials: P
authors.lastname: Novák
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D000225:Adenine / Q000138:chemical synthesis / Q000737:chemistry; D001483:Base Sequence; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013941:Thymine / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides; D009841:Oligonucleotides; D063065:Organophosphonates; D004259:DNA-Directed DNA Polymerase; D000225:Adenine; D013941:Thymine