期刊
NATURE CHEMISTRY
卷 3, 期 11, 页码 875-881出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.1151
关键词
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资金
- Robert A. Welch Foundation [F1188, F1604, AF-0005]
- National Institutes of Health [GM-069647]
- American Chemical Society
- Southwestern University faculty
A long-lived and sequence-specific ligand-DNA complex would make possible the modulation of biological processes for extended periods. For this purpose, we are investigating a polyintercalation approach to DNA recognition in which flexible chains of aromatic units thread back and forth repeatedly through the double helix. Here we describe the DNA-binding behaviour of a threading tetra-intercalator. Specific binding was observed on a relatively long DNA strand that strongly favoured a predicted 14 base-pair sequence. Kinetic studies revealed a multistep association process, with sequence specificity that primarily derives from large differences in dissociation rates. The rate-limiting dissociation rate constant of the tetra-intercalator complex dissociating from its preferred binding site was extremely slow, corresponding to a half-life of 16 days. This is one of the longest non-covalent complex half-lives yet reported and, to the best of our knowledge, the longest for a DNA-binding molecule.
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