Oligonucleotides containing 2-aminoadenine and 2-thiothymine act as selectively binding complementary agents

Biochemistry. 1996 Aug 27;35(34):11170-6. doi: 10.1021/bi960626v.

Abstract

A pair of complementary oligodeoxynucleotides (ODNs) uniformly substituted with 2-amino-adenine (A') in place of adenine and 2-thiothymine (T') in place of thymine did not hybridize to each other but did form very stable hybrids with unmodified complementary ODNs. These unusual properties were a consequence of the hydrogen-bonding properties of the two base analogs. Thermal denaturation studies of short duplexes which contained these bases demonstrated that the A'-T and A-T' doublets formed stable base pairs whereas the A'-T' doublet acted like a mismatch. Complementary ODNs substituted with these base analogs are referred to as SBC or selectively binding complementary ODNs. When used as a pair, these single-stranded ODNs invaded the ends of homologous duplexes and formed stable three-arm junctions under conditions where unmodified ODNs failed to give a product. SBC ODNs have a fundamental thermodynamic advantage in hybridizing to short segments of double-stranded nucleic acid and represent a new approach for the design of oligomeric probes and antisense agents. Many secondary structure features present in long single-stranded nucleic acids should be accessible to these reagents.

MeSH terms

  • 2-Aminopurine / analogs & derivatives*
  • 2-Aminopurine / metabolism
  • Base Sequence
  • Electrophoresis, Polyacrylamide Gel
  • Hydrogen Bonding
  • Molecular Sequence Data
  • Molecular Structure
  • Nucleic Acid Conformation*
  • Nucleic Acid Denaturation
  • Nucleic Acid Hybridization*
  • Oligodeoxyribonucleotides / metabolism*
  • Thermodynamics
  • Thymine / analogs & derivatives*
  • Thymine / metabolism

Substances

  • Oligodeoxyribonucleotides
  • 2-Aminopurine
  • 2,6-diaminopurine
  • 2-thiothymine
  • Thymine