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 derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (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.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.
A V
AV
Feofanov
A V
AV
Baranov
F
F
Fleury
J F
JF
Riou
I R
IR
Nabiev
M
M
Manfait
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism*; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism*; D000077146:Irinotecan; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D013539:Simian virus 40; D013059:Spectrum Analysis, Raman; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin