Abstract
We have used DNase I footprinting to study the binding strength and DNA sequence selectivity of novel derivatives of the quinoxaline bis-intercalator TANDEM. Replacing the valine residues in the cyclic octadepsipeptide with lysines does not affect the selectivity for TpA but leads to a 50-fold increase in affinity. In contrast, replacing both of the quinoxaline chromophores with naphthalene rings abolishes binding, while changing a single ring decreases the affinity, and footprints are observed at only the best binding sites (especially TATATA). By using fragments with different lengths of [(AT) n ], we demonstrate that these ligands bind best to the center of the longer (AT) n tracts.
Original language | English |
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Pages (from-to) | 7900-7906 |
Number of pages | 7 |
Journal | Biochemistry |
Volume | 47 |
Issue number | 30 |
DOIs | |
Publication status | Published - 1 Jul 2008 |
Keywords
- Binding Sites
- DNA/chemistry
- DNA Footprinting
- Deoxyribonuclease I/metabolism
- Intercalating Agents/chemistry
- Lysine/chemistry
- Models, Molecular
- Naphthalenes/chemistry
- Quinoxalines/chemistry
- Valine/chemistry