| Attributs | Valeurs |
|---|
| type
| |
| Is Part Of
| |
| Subject
| |
| Title
| - Quinoxaline Antibiotics Enhance Peptide Nucleic Acid Binding to Double-StrandedDNA
|
| has manifestation of work
| |
| related by
| |
| Author
| |
| Abstract
| - The effects of a wide range of DNA binding drugs on peptide nucleic acid (PNA) binding todouble-stranded DNA by strand displacement have been investigated using a gel retardation assay. Thebis-PNA [H-(Lys)-TTJTTJTTTT-(eg)3-TTTTCTTCTT-Lys-NH2] was used together with a 248 bp DNAfragment containing an appropriate target for the PNA. Most of the ligands that were studied, includingDNA minor groove binders as well as intercalators and bis-intercalators, either have no effect or stronglyinhibit PNA binding to DNA. By contrast, quinoxaline antibiotics facilitate PNA−DNA complex formation.The “PNA-helper” effect of echinomycin was studied in more detail using time and temperature dependenceexperiments to elucidate the mechanism. PNA binding to DNA follows pseudo-first-order kinetics, butthe initial rate of binding is accelerated more than 10-fold in the presence of 10 μM echinomycin. Theactivation energy for PNA binding to dsDNA is lowered 2-fold by the antibiotic (45 vs 90 kJ/mol in thecontrol). The reasons why quinoxalines promote the binding of PNA to DNA are not entirely clear butmay well include distortions (opening) of the double helix that facilitate PNA invasion. This studyestablishes that the efficacy of DNA-targeted PNA antigene molecules could potentially be enhanced byjudiciously adding certain DNA-interactive ligands.
|
| article type
| |
| is part of this journal
| |
