Stable and selective formation of hoogsteen-type triplexes and duplexes using twisted intercalating nucleic acids (TINA) prepared via postsynthetic Sonogashira solid-phase coupling reactions

J Am Chem Soc. 2005 Oct 26;127(42):14849-58. doi: 10.1021/ja053645d.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzyl Compounds / chemistry*
  • Glycerol / analogs & derivatives
  • Glycerol / chemistry
  • Molecular Structure
  • Oligodeoxyribonucleotides* / chemical synthesis
  • Oligodeoxyribonucleotides* / chemistry
  • Propanols / chemistry*
  • Pyrenes / chemistry
  • Pyrimidines / chemistry*
  • Spectrophotometry, Ultraviolet
  • Temperature

Substances

  • (R)-1-O-(4-(1-pyrenylethynyl)phenylmethyl)glycerol
  • (S)-1-(4,4'-dimethoxytriphenylmethyloxy)-3-(4-iodo-benzyloxy)-propan-2-ol
  • Benzyl Compounds
  • Oligodeoxyribonucleotides
  • Propanols
  • Pyrenes
  • Pyrimidines
  • Glycerol