title: Synthesis and triplex-forming properties of oligonucleotides capable of recognizing corresponding DNA duplexes containing four base pairs.
abstract: A triplex-forming oligonucleotide (TFO) could be a useful molecular tool for gene therapy and specific gene modification. However, unmodified TFOs have two serious drawbacks: low binding affinities and high sequence-dependencies. In this paper, we propose a new strategy that uses a new set of modified nucleobases for four-base recognition of TFOs, and thereby overcome these two drawbacks. TFOs containing a 2'-deoxy-4N-(2-guanidoethyl)-5-methylcytidine (d(g)C) residue for a C-G base pair have higher binding and base recognition abilities than those containing 2'-OMe-4N-(2-guanidoethyl)-5-methylcytidine (2'-OMe (g)C), 2'-OMe-4N-(2-guanidoethyl)-5-methyl-2-thiocytidine (2'-OMe (g)Cs), d(g)C and 4S-(2-guanidoethyl)-4-thiothymidine ((gs)T). Further, we observed that N-acetyl-2,7-diamino-1,8-naphtyridine ((DA)Nac) has a higher binding and base recognition abilities for a T-A base pair compared with that of dG and the other DNA derivatives. On the basis of this knowledge, we successfully synthesized a fully modified TFO containing (DA)Nac, d(g)C, 2'-OMe-2-thiothymidine (2'-OMe (s)T) and 2'-OMe-8-thioxoadenosine (2'-OMe (s)A) with high binding and base recognition abilities. To the best of our knowledge, this is the first report in which a fully modified TFO accurately recognizes a complementary DNA duplex having a mixed sequence under neutral conditions.
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan aohkubo@bio.titech.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohkubo
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Miyauchi
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanamori
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Masaki
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Seio
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Yuasa
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan msekine@bio.titech.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sekine
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; C051802:triplex DNA; D004247:DNA