title: Stable and selective formation of hoogsteen-type triplexes and duplexes using twisted intercalating nucleic acids (TINA) prepared via postsynthetic Sonogashira solid-phase coupling reactions.
abstract: Bulge insertions of (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol (5) into the middle of homopyrimidine oligodeoxynucleotides (twisted intercalating nucleic acids, TINA) obtained via postsynthetic Sonogashira coupling reaction led to extraordinary high thermal stability of Hoogsteen-type triplexes and duplexes, whereas Watson-Crick-type duplexes of the same nucleotide content were destabilized. Modified oligonucleotides were synthesized using the phosphoramidite of (S)-1-(4,4'-dimethoxytriphenylmethyloxy)-3-(4-iodo-benzyloxy)-propan-2-ol followed by treatment of the oligonucleotide on a CPG-support with the Sonogashira-coupling reaction mixture containing different ethynylaryls. Bulged insertion of the pyrene derivative 5 into oligonucleotides was found to be the best among the tested modifications for binding to the Hoogsteen-type triplexes and duplexes. Thus, at pH 7.2 an oligonucleotide with cytidine content of 36% possessing two bulged insertions of 5 separated by three bases formed a stable triplex (T(m) = 43.0 degrees C), whereas the native oligonucleotide was unable to bind to the target duplex. The corresponding Watson-Crick-type duplex with the same oligonucleotide had T(m) of 38.0 degrees C at pH 7.2, while the T(m) of unmodified dsDNA was 47.0 degrees C. Experiments with mismatched oligonucleotides, luminescent properties, and potential applications of TINA technology is discussed.
authors.affiliation: Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Vyacheslav V
authors.initials: VV
authors.lastname: Filichev
authors.forename: Erik B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D001593:Benzyl Compounds / Q000737:chemistry*; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D020005:Propanols / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: C507245:(R)-1-O-(4-(1-pyrenylethynyl)phenylmethyl)glycerol; C507244:(S)-1-(4,4'-dimethoxytriphenylmethyloxy)-3-(4-iodo-benzyloxy)-propan-2-ol; D001593:Benzyl Compounds; D009838:Oligodeoxyribonucleotides; D020005:Propanols; D011721:Pyrenes; D011743:Pyrimidines; D005990:Glycerol