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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.
LanguageEnglish
Pages3410-3417
Number of pages7
JournalNucleic Acids Research
Volume32
Issue number11
DOIs
Publication statusPublished - 5 Jun 2004

Fingerprint

Thiazoles
Nylons
Ligands
Freezing
DNA Footprinting
DNA
Oligonucleotides
Fluorescence

Keywords

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

Cite this

James, P. L., Merkina, E. E., Khalaf, A. I., Suckling, C. J., Waigh, R. D., Brown, T., & Fox, K. R. (2004). DNA sequence recognition by an isopropyl substituted thiazole polyamide. Nucleic Acids Research, 32(11), 3410-3417. https://doi.org/10.1093/nar/gkh666
James, P.L. ; Merkina, E.E. ; Khalaf, A.I. ; Suckling, C.J. ; Waigh, R.D. ; Brown, T. ; Fox, K.R. / DNA sequence recognition by an isopropyl substituted thiazole polyamide. In: Nucleic Acids Research. 2004 ; Vol. 32, No. 11. pp. 3410-3417.
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James, PL, Merkina, EE, Khalaf, AI, Suckling, CJ, Waigh, RD, Brown, T & Fox, KR 2004, 'DNA sequence recognition by an isopropyl substituted thiazole polyamide' Nucleic Acids Research, vol. 32, no. 11, pp. 3410-3417. https://doi.org/10.1093/nar/gkh666

DNA sequence recognition by an isopropyl substituted thiazole polyamide. / James, P.L.; Merkina, E.E.; Khalaf, A.I.; Suckling, C.J.; Waigh, R.D.; Brown, T.; Fox, K.R.

In: Nucleic Acids Research, Vol. 32, No. 11, 05.06.2004, p. 3410-3417.

Research output: Contribution to journalArticle

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T1 - DNA sequence recognition by an isopropyl substituted thiazole polyamide

AU - James, P.L.

AU - Merkina, E.E.

AU - Khalaf, A.I.

AU - Suckling, C.J.

AU - Waigh, R.D.

AU - Brown, T.

AU - Fox, K.R.

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AB - 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.

KW - DNA sequence

KW - isopropyl substituted thiazole polyamide

KW - fluorescence melting

KW - groove binding ligand

KW - tetranucleotide sequence

KW - fluorescently labelled oligonucleotides

KW - applied chemistry

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DO - 10.1093/nar/gkh666

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