title: Development of artificial nucleic acid that recognizes a CG base pair in triplex DNA formation.
abstract: An oligonucleotide that can form a triplex with double-stranded DNA is called a triplex-forming oligonucleotide (TFO). TFOs have gained considerable attention because of their potential as gene targeting tools. However, triplex DNA formation involves inherent problems for practical use. The most important problem is that natural nucleotides in TFO do not have sufficient affinity and base pair-selectivity to pyrimidine-purine base pair, like a CG or TA base pair, within dsDNA. This suggests that dsDNA region including a CG or TA base pair cannot be targeted. Therefore, artificial nucleotides, especially with non-natural nucleobases, capable of direct recognition of a CG or TA base pair via hydrogen bond formation have been developed; however, nucleotides with better selectivity and stronger affinity are necessary for implementing this dsDNA-targeting technology using TFOs. Under such a background, we considered that facile and efficient synthesis of various nucleobase derivatives in TFOs would be useful for finding an ideal nucleobase for recognition of a CG or TA base pair because detailed and rational exploration of nucleobase structures is facilitated. Recently, to develop a nucleobase recognizing a CG base pair, we have used post-elongation modification, i.e., modification after oligonucleotide synthesis, for the facile synthesis of nucleobase derivatives. This review mainly summarizes our recent findings on the development of artificial nucleobases and nucleotides for recognition of a CG base pair in triplexes formed between dsDNA and TFOs.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hari
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D009696:Nucleic Acids / Q000737:chemistry*; D044366:Transition Temperature
chemical_list: D009696:Nucleic Acids; C051802:triplex DNA; D004247:DNA