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© Yang SI, Institut Pasteur
Publication : Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie

Targeting topoisomerase I cleavage to specific sequences of DNA by triple helix-forming oligonucleotide conjugates. A comparison between a rebeccamycin derivative and camptothecin

Team: Epigenetic Chemical Biology
Member: Paola Arimondo
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie - 01 Sep 1999

Arimondo PB, Bailly C, Boutorine A, Sun JS, Garestier T, Hélène C

Link to Pubmed [PMID] – 10547719

C. R. Acad. Sci. III, Sci. Vie 1999 Sep;322(9):785-90

Topoisomerase I is an ubiquitous DNA cleaving enzyme and an important therapeutic target in cancer chemotherapy for the camptothecins as well as for indolocarbazole antibiotics such as rebeccamycin and its synthetic derivatives, which stabilize the cleaved DNA-topoisomerase I complex. The covalent linkage of a triple helixforming oligonucleotide to camptothecin or to the indolocarbazole derivative R-6 directs DNA cleavage by topoisomerase I to specific sequences. Sequence-specific recognition of DNA is achieved by the triple helix-forming oligonucleotide, which binds to the major groove of double-helical DNA and positions the drug at a specific site. The efficacy of topoisomerase I-induced DNA cleavage mediated by the rebeccamycin-conjugate and the camptothecin-conjugate was compared and related to the intrinsic potency of the isolated drugs.