DNA TOPOISOMERASE-I CHANGES THE MODE OF INTERACTION BETWEEN CAMPTOTHECIN DRUGS AND DNA AS PROBED BY UV-RESONANCE RAMAN-SPECTROSCOPY

Pronounced differences of interactions of camptothecin (CPT) and its d erivative 1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT11), inhibitors of DNA topoisomerase I, with oligonucleotides were found us ing UV resonance Raman spectroscopy. 30-mer oligonucleotides were deri ved from the sequences of the topoisomerase I-induced and CPT-enhanced cleavage sites in SV40 DNA, CPT induces well-defined alterations of t he 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 fou nd for its parent compound CPT, and enhances this interaction as compa red to CPT-oligonucleotide complexes, The data present evidence of mol ecular interactions of CPT11 with both other partners (topoisomerase I and oligonucleotide) of the ternary cleavable complex at the oligonuc leotide-enzyme interface.