The G.C base-pair preference of 2-N-methyl 9-hydroxyellipticinium
| Autor: | Christian Auclair, Jean Aubard, Guy Dodin, Marc-Antoine Schwaller, Claude Paoletti |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Guanine
Stereochemistry Base pair Fluorescence spectrometry Quantum yield Biochemistry Nucleobase chemistry.chemical_compound Cytosine Alkaloids Polydeoxyribonucleotides Poly dA-dT Nucleotide Ellipticines Binding site chemistry.chemical_classification Base Composition DNA Models Theoretical Fluorescence Intercalating Agents Kinetics Spectrometry Fluorescence chemistry Energy Transfer Nucleic Acid Conformation |
| Zdroj: | European journal of biochemistry. 181(1) |
| ISSN: | 0014-2956 |
| Popis: | Among the DNA-intercalating drugs in the ellipticinium series, 9-hydroxy derivatives elicit the highest antitumoral properties. In water these drugs display a very low fluorescence quantum yield. Replacement of H2O by D2O partially restores the fluorescence of the ellipticinium chromophore. The possibility that such a proton-exchange mechanism could be involved in a base-recognizing process at the DNA level (and therefore be responsible for some base preference) was examined by direct fluorescence titration in deuterated buffer and DNA/drug fluorescence energy transfer. These experimental approaches provide mutually consistent results showing that the 9-hydroxylated drug recognizes specific DNA sites that are not recognized by the non-hydroxylated drug. When compared to 2-N-methyl ellipticinium, the 2-N-methyl 9-hydroxyellipticinium presents: (1) higher binding constants for each DNA studied; (2) a base dependence of the fluorescence properties of the bound form (fluorescence increment upon DNA binding varying over 5–11); (3) a base dependence of its DNA affinity constants (1.1–3.3 × 106 M−1) and of its site size (exclusion parameters varying over 3.0-4.4); (4) a base dependence of its energy transfer from DNA bases. Analysis of the binding data suggests that the 9-hydroxyl group of 2-N-methyl ellipticinium is responsible for a G · C base-pair preference, the preferred binding site being a doublet sequence of two adjacent G · C which could be flanked either by a additional G · C base pair or by an A · T base pair. |
| Databáze: | OpenAIRE |
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