Irreversible trapping of the DNA-topoisomerase I covalent complex. Affinity labeling of the camptothecin binding site.

Hertzberg, Robert; Busby, Robert; Caranfa, Mary Jo; Holden, Kenneth G.; Johnson, Randall K.; Hecht, Sidney M.; Kingsbury, William D.

doi:10.1016/s0021-9258(17)30656-7

Cited by 97 publications

(40 citation statements)

References 35 publications

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“…Camptothecin ( Scheme 1 ), 4-ethyl-4-hydroxy-(S)-1-H-Pyrano [3′,4′:6,7] indolizino [ 1 , 2 – 6 ] quinolino-3,14 (4H,12H)-dione, the active compound of Camptotheca acuminate [ 1 ], is a well-known antitumor drug for gastric cancer [ 2 ], breast cancer [ 3 ] and lung cancer [ 4 ]. Its primary cellular target is topoisomerase I, and the antitumor activity is attributed to the inhibition of topoisomerase I [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Its primary cellular target is topoisomerase I, and the antitumor activity is attributed to the inhibition of topoisomerase I [ 5 ]. As a topoisomerase I “poison”, camptothecin can bind both DNA and topoisomerase I to form a stable ternary complex [ 6 , 7 ], which prevents DNA synthesis and induces the death of cells. Meanwhile, it has also exhibited some other biological activities, such as anti-HIV [ 8 ] and against parasitic trypanosomes and Leishmania [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Electrochemical Studies of Camptothecin and Its Interaction with Human Serum Albumin

Zhao

Zheng

Wang

et al. 2007

IJMS

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Camptothecin, an anticancer component from Camptotheca acuminate, may interact with human serum albumin (HSA) at the subdomain IIA (site I), and then convert to its inactive form(carboxylate form). In this paper, the detailed electrochemical behaviors of camptothecin at a pyrolytic graphite electrode is presented. The interaction between camptothecin and HSA is also studied by electrochemical technique. By comparing with bovine serum albumin (BSA), which is highly homologous to HSA, we prove that camptothecin can specifically bind to HSA. Meanwhile, the inhibitory influence of sodium salicylate to this binding is also discussed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electrochemical Studies of Camptothecin and Its Interaction with Human Serum Albumin

Zhao

Zheng

Wang

et al. 2007

IJMS

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“…Camptothecin stabilizes the covalent topoisomerase I-DNA cleavable complex by preventing DNA religation (23,24). Previous binding studies with radiolabeled CPT indicated that camptothecin forms a ternary complex in which it is bound noncovalently to the covalent enzyme-DNA binary complex (34). While the exact structure of the ternary complex is not known, the available evidence suggests that CPT must bind at the interface formed between protein and DNA in the binary complex since one type of electrophilic CPT analogue (having a reactive functionality at position 10) alkylated the enzyme (34), while a second electrophilic CPT analogue (reactive functionality at position 7) alkylated the G at position +1 on the scissile strand (35,36).…”

Section: Discussionmentioning

confidence: 99%

“…Previous binding studies with radiolabeled CPT indicated that camptothecin forms a ternary complex in which it is bound noncovalently to the covalent enzyme-DNA binary complex (34). While the exact structure of the ternary complex is not known, the available evidence suggests that CPT must bind at the interface formed between protein and DNA in the binary complex since one type of electrophilic CPT analogue (having a reactive functionality at position 10) alkylated the enzyme (34), while a second electrophilic CPT analogue (reactive functionality at position 7) alkylated the G at position +1 on the scissile strand (35,36). On the basis of the observed sequence preference for guanosine at position +1 for efficient topoisomerase I cleavage, Leteurtre et al (26) have proposed that the planar, heterocyclic ring system of camptothecin interacts, possibly through hydrogen bonding or stacking interactions, with the nucleobase at position +1 on the scissile strand.…”

Section: Discussionmentioning

confidence: 99%

DNA Topoisomerase I-Mediated Formation of Structurally Modified DNA Duplexes. Effects of Metal Ions and Topoisomerase I Inhibitors

1998

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The ability of DNA topoisomerase I to mediate the formation of structurally modified DNA duplexes was studied utilizing suicide substrates containing high-efficiency cleavage sites and acceptor oligonucleotides in which the 5'-terminal nucleotides were varied. When the substrates were nicked duplexes, the divalent cations Mg2+ and Ca2+ were found to facilitate the topoisomerase I-mediated formation of ligation products containing 3-nucleotide deletions on the scissile strand, but to suppress the formation of 1-nucleotide deletions. The presence of a complementary nucleotide at the 5'-end of the acceptor strand was not required for the ligation reaction to proceed, but duplex formation to produce duplexes containing a mismatch proceeded more slowly than formation of the fully complementary duplex. Topoisomerase I-mediated mismatch formation in the ligation reaction was inhibited more readily by camptothecin than the corresponding ligation reaction to form a fully complementary duplex; the extent of inhibition was comparable for all three mismatches studied. In comparison, the topoisomerase I inhibitors nitidine and coralyne exhibited quite different effects on the same ligation reactions.

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“…Camptothecin cannot bind to isolated DNA alone; however, it binds reversibly to topo I ±DNA complexes. 41 Camptothecin is able to form ternary complexes with the enzyme and the DNA in all stages of the cell cycle, while the cytotoxicity of the drug is Sphase ± specific. 11 This indicates that, although the formation of such ternary complexes has been related to the mechanism of cell killing, 19,42 the formation of the drug ±enzyme ±DNA ternary complex by itself is insufficient for cell killing.…”

Section: Topo Poisonsmentioning

confidence: 99%

Dual topoisomerase I/II inhibitors

Gijn

Lendfers

Schellens

et al. 2000

J Oncol Pharm Pract

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Topoisomerase (topo) I and II are nuclear enzymes, which play a major role in the topological rearrangement of DNA during replication and transcription processes. In the course of years, many different agents have been found which can inhibit the topos and thereby exploit cytotoxicity, also against tumour cells. Selective inhibition of the topo I enzyme can, however, induce a reactive increase in topo II levels, and vice versa. This mechanism is associated with the development of drug resistance. Dual inhibition of both topo I and II may, theoretically, overcome this resistance problem. In this review, the most important and promising dual topo I/II inhibitors designed as anticancer agents will be discussed. Thus far, only the indolyl quinoline derivative TAS-103, the 7 H-benzo [ e] pyrido [4,3- b] indole derivative intoplicine, and the acridine derivative PZA have been shown to be dual topo inhibitors with high cytotoxicity.

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Irreversible trapping of the DNA-topoisomerase I covalent complex. Affinity labeling of the camptothecin binding site.

Cited by 97 publications

References 35 publications

Electrochemical Studies of Camptothecin and Its Interaction with Human Serum Albumin

Electrochemical Studies of Camptothecin and Its Interaction with Human Serum Albumin

DNA Topoisomerase I-Mediated Formation of Structurally Modified DNA Duplexes. Effects of Metal Ions and Topoisomerase I Inhibitors

Dual topoisomerase I/II inhibitors

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