DNA sequence recognition by an isopropyl substituted thiazole polyamide

P.L. James, E.E. Merkina, A.I. Khalaf, C.J. Suckling, R.D. Waigh, T. Brown, K.R. Fox

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Abstract

We have used DNA footprinting and fluorescence melting experiments to study the sequence-specific binding of a novel minor groove binding ligand (thiazotropsin A), containing an isopropyl substituted thiazole polyamide, to DNA. In one fragment, which contains every tetranucleotide sequence, sub-micromolar concentrations of the ligand generate a single footprint at the sequence ACTAGT. This sequence preference is confirmed in melting experiments with fluorescently labelled oligonucleotides. Experiments with DNA fragments that contain variants of this sequence suggest that the ligand also binds, with slightly lower affinity, to sequences of the type XCYRGZ, where X is any base except C, and Z is any base except G.
Original languageEnglish
Pages (from-to)3410-3417
Number of pages7
JournalNucleic Acids Research
Volume32
Issue number11
DOIs
Publication statusPublished - 5 Jun 2004

Keywords

  • DNA sequence
  • isopropyl substituted thiazole polyamide
  • fluorescence melting
  • groove binding ligand
  • tetranucleotide sequence
  • fluorescently labelled oligonucleotides
  • applied chemistry

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