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

被引：26

作者：

Arimondo, PB

Bailly, C

Boutorine, A

Sun, JS

Garestier, T

Hélène, C

机构：

[1] Museum Natl Hist Nat, INSERM, U201, UMR 8646 CNRS,Lab Biophys, F-75231 Paris, France

[2] IRCL, INSERM, U524, F-59045 Lille, France

[3] IRCL, Ctr Oscar Lambret, Lab Pharmacol Antitumorale, F-59045 Lille, France

来源：

COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES | 1999年 / 322卷 / 09期

关键词：

topoisomerase I; triple helix-forming oligonucleotides; sequence-specific DNA cleavage; topoisomerase I inhibitors;

D O I：

10.1016/S0764-4469(00)80037-2

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 helix-forming 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. (C) 1999 Academie des sciences/Editions scientifiques et medicales Elsevier SAS.

引用

页码：785 / 790

页数：6

共 18 条

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[2]

ARIMONDO PB, 1999, IN PRESS BIOORG MED

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