Subtle recognition of 14-base pair DNA sequences via threading polyintercalation
| Autor: | Brian Aki Ikkanda, Amy Madison Rhoden Smith, Garen G. Holman, Brent L. Iverson |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Base pair Stereochemistry DNA Footprinting DNA footprinting Naphthalenes 010402 general chemistry Imides 01 natural sciences Biochemistry Article chemistry.chemical_compound Directionality Deoxyribonuclease I Base Pairing Binding Sites Base Sequence 010405 organic chemistry Chemistry DNase-I Footprinting DNA Intercalating Agents 0104 chemical sciences DNA binding site Nucleic Acid Conformation Threading (protein sequence) |
| Zdroj: | Biochemistry |
| ISSN: | 1520-4995 |
| Popis: | Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading polyintercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator composed of alternating minor-major-minor groove-binding modules was shown to bind specifically to a 14 bp DNA sequence with a dissociation half-life of 16 days [Holman, G. G., et al. (2011) Nat. Chem. 3, 875-881]. Herein are described new NDI-based tetraintercalators with a different major groove-binding module and a reversed N to C directionality of one of the minor groove-binding modules. DNase I footprinting and kinetic analyses revealed that these new tetraintercalators are able to discriminate, by as much as 30-fold, 14 bp DNA binding sites that differ by 1 or 2 bp. Relative affinities were found to correlate strongly with dissociation rates, while overall C(2) symmetry in the DNA-binding molecule appeared to contribute to enhanced association rates. |
| Databáze: | OpenAIRE |
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