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DNA topoisomerase I changes the mode of interaction between camptothecin drugs and DNA as probed by UV-resonance Raman spectroscopy

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Feofanov, Alexei | Baranov, Alexandre | Fleury, Fabrice | Riou, Jean-François | Nabiev, Igor | Manfait, Michel

Edité par CCSD ; Wiley -

International audience. Pronounced differences of interactions of camptothecin (CPT) and its derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloycamptothecin (CPT11), inhibitors of DNA topoisomerase I, with oligonucleotides were found using UV resonance Raman spectroscopy. 30-mer oligonucleotides were derived from the sequences of the topoisomerase I-induced and CPT-enhanced cleavage sites in SV40 DNA. CPT induces well-defined alterations of the oligo structure, whereas CPT11 interacts with oligonucleotides more weakly and in another manner than CPT. Formation of cleavable ternary complexes between CPT11, topoisomerase I and oligonucleotides causes CPT11 to interact with oligonucleotides in the same fashion as was found for its parent compound CPT, and enhances this interaction as compared to CPT-oligonucleotide complexes. The data present evidence of molecular interactions of CPT11 with both other partners (topoisomerase I and oligonucleotide) of the ternary cleavable complex at the oligonucleotide-enzyme interface.

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