Published online 24 June 2004
Nucleic Acids Research, Vol. 32 No. 11 © Oxford University Press 2004; all rights reserved
DNA sequence recognition by an isopropyl substituted thiazole polyamide
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK, 1 Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK, 2 Department of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK and 3 Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
* To whom correspondence should be addressed. Tel: +44 23 8059 4374; Fax: +44 23 8059 4459; Email: krf1{at}soton.ac.uk
Received April 22, 2004; Revised and Accepted June 5, 2004
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.