The binding of bridged bis-pyridinium oximes to DNA and its relevance to the induction of mitochondrial dysfunction in yeast

Autor: Sylvano Nocentini, Pierre Demerseman, Guy Dodin, Jean-Marc Kühnel, Dietrich Averbeck
Rok vydání: 1992
Předmět:
Zdroj: Biochemical and biophysical research communications. 186(3)
ISSN: 0006-291X
Popis: Summary Bis-pyridium oximes and methoximes from a newly synthesized series are weak DNA binders (K= 3.104 M−1 under physiological conditions). From the number of binding sites per phosphate, 0.25, the ionic strength dependence of the binding constant and the negative electric dichroism, it is concluded that monointercalation is the mode of association. In contrast to methoxy compounds, the oxime derivatives are able both to induce the mutated “petite” phenotype in yeast S. cerivisiae and to cause “in vitro” extensive condensation of single stranded DNA. This reaction is postulated to be relevant to the mutational process that leads to “petite” cells. The absence of nuclear mutation is interpreted in terms of sequestration of the drug in mitochondria under the effect of the organelle inner membrane electrochemical potential.
Databáze: OpenAIRE
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