Kinetic studies on the formation of DNA triplexes containing the nucleoside analogue 2'-O-(2-aminoethyl)-5-(3-amino-1-propynyl)uridine

David A. Rusling, Victoria J. Broughton-Head, Alex Tuck, Hannah Khairallah, Sadie D. Osborne, Tom Brown, Keith R. Fox

Research output: Contribution to journalArticlepeer-review


We have examined the kinetics of triple helix formation of oligonucleotides that contain the nucleotide analogue 2'-O-(2-aminoethyl)-5-(3-amino-1-propynyl)uridine (bis-amino-U, BAU), which forms very stable base triplets with AT. Triplex stability is determined by both the number and location of the modifications. BAU-containing oligonucleotides generate triplexes with extremely slow kinetics, as evidenced by 14 degrees C hysteresis between annealing and melting profiles even when heated at a rate as slow as 0.2 degrees C min(-1). The association kinetics were measured by analysis of the hysteresis profiles, temperature-jump relaxation and DNase I footprinting. We find that the slow kinetics are largely due to the decreased rate of dissociation; BAU modification has little effect on the association reaction. The sequence selectivity is also due to the slower dissociation of BAU from AT than other base pairs.

Original languageEnglish
Pages (from-to)122-129
Number of pages8
JournalOrganic & Biomolecular Chemistry
Issue number1
Early online date1 Nov 2007
Publication statusPublished - 7 Jan 2008


  • Base Pair Mismatch
  • Base Sequence
  • DNA/chemistry
  • Deoxyribonuclease I/chemistry
  • Fluorescence
  • Kinetics
  • Oligonucleotides/chemistry
  • Peptide Mapping
  • Temperature
  • Time Factors
  • Transition Temperature
  • Uridine/analogs & derivatives


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