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

Abstract

Pronounced differences of interactions of camptothecin (CPT) and its derivative 7-ethyl-10-[4-(1-piperidino)-lpiperidino]carbonyloxycamptothecin (CPTll), 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 CPTll interacts with oligonucleotides more weakly and in another manner than CPT. Formation of cleavable ternary complexes between CPTll, topoisomerase I and oligonucleotides causes CPTll 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 CPTll with both other partners (topoisomerase I and oligonucleotide) of the ternary cleavable complex at the oligonucleotide-enzyme interface.

The influence of divalent metal ions on low pH induced LacDNA structural changes as probed with UV resonance Raman spectroscopy

“…UV resonance Raman wavenumbers (cm À1 ) and tentative assignments of LacDNA complexes in different physico-chemical conditions, of the corresponding single-stranded oligonucleotides and of the proper sum of spectra of single oligonucleotides. [1,5,11,19,20,[23][24][25][26][27][28][29][30][31][32] Raman spectra were excited with a 275 nm laser line. The spectral resolution was appreciated to be 3 cm Intensity changes can also give insight into changes in coupling or electronic structure.…”

“…Besides, dA and dG residues were also found to contribute to this band. [23,26,27,32] Very informative is the guanine band at 1490 cm À1 , which decreases in intensity upon binding of electrophilic agents to the N7 acceptor of guanine. [1,19,23] This vibration is known to be very sensitive to any ligation or complexation involving the N7 ([Ref.…”

“…Wavenumber positions of the major peaks are presented in Figs 3 and 4, respectively, being in accordance with those given previously in the literature. [1,5,11,19,20,[23][24][25][26][27][28][29][30][31][32] Table 1 presents a detailed comparative analysis of the UV (275 nm) resonance Raman markers of the six LacDNA complexes, the corresponding single-stranded oligonucleotides (SS1 and SS2) and the proper sum of spectra of single oligonucleotides. Proposed UVRR band assignments found in the literature for similar compounds are also included.…”

CPT11 prevents virus replication in JCI cells persistently infected with JC polyomavirus

“…A previous study demonstrated that inhibitors of topoisomerase strongly suppress SV40 DNA replication , suggesting that topoisomerase I is required for efficient SV40 replication. CPT reportedly induces remarkable alternations of oligonucleotides containing the sequences of the topoisomerase I‐induced and CPT‐enhanced cleavage sites in SV40 DNA, whereas CPT11 interacts more weakly and in a different manner than CPT . It is possible that CPT11 forms a ternary complex with topoisomerase I and JCPyV DNA by binding reversibly at DNA cleavage sites.…”

“…Moreover, treatment with topotecan or β‐lapachone results in marginal inhibition of viral propagation in JCI cells, which produce high titers of JCPyV, according to RT‐PCR analysis . In contrast, UV resonance Raman spectroscopy using oligonucleotides derived from the sequences of topoisomerase I‐induced and CPT‐enhanced cleavage sites in SV40 DNA showed differences in the interactions of CPT and CPT11 . This report led us to seek other topoisomerase inhibitors of JCPyV, a synthesized CPT derivative that has been shown to be associated with inhibition of topoisomerase I.…”