title: Regiospecific inhibition of DNA duplication by antisense phosphate-methylated oligodeoxynucleotides.
abstract: A new synthesis route for long phosphate-methylated oligodeoxynucleotides is described, which were used as antisense inhibitors of the DNA replication. Phosphate-methylated oligomers hybridize more strongly with natural DNA than their natural analogues, due to the absence of electrostatic interstrand repulsions. Compared with phosphate-ethylated and methyl phosphonate systems, phosphate-methylated systems are preferable as antisense DNA, which was concluded from the high Tm values and sharp melting transitions of duplexes of phosphate-methylated and natural DNA. By using the Sanger dideoxy technique, it was shown that a complementary phosphate-methylated 18-mer can effectively and site-specifically block the DNA replication process at room temperature.
authors.affiliation: Department of Organic Chemistry, Eindhoven University of Technology, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Moody
authors.forename: M H
authors.initials: MH
authors.lastname: van Genderen
authors.forename: L H
authors.initials: LH
authors.lastname: Koole
authors.forename: H J
authors.initials: HJ
authors.lastname: Kocken
authors.forename: E M
authors.initials: EM
authors.lastname: Meijer
authors.forename: H M
authors.initials: HM
authors.lastname: Buck
mesh_terms: D001483:Base Sequence; D004261:DNA Replication / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D013698:Templates, Genetic
chemical_list: D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D010710:Phosphates