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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
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pubmed:dateCreated |
1998-7-23
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pubmed:abstractText |
The effects of eleven camptothecin derivatives on calf thymus topoisomerase I-mediated cleavage of synthetic DNA duplex have revealed that the A ring of camptothecin is very important for its biochemical activity. Depending on the type, number, and location of substituents, highly active or inactive analogues were obtained. The persistence of CPT-induced topoisomerase I-DNA covalent binary complexes was investigated by using as substrates DNA containing several good topoisomerase I cleavage sites, or else a synthetic DNA duplex of defined structure with a single high-efficiency cleavage site. The ligation kinetics at a given topoisomerase I cleavage site were sometimes quite different in the presence of CPT derivatives whose structures were closely related. Even in the presence of a single CPT analogue, topoisomerase I-DNA covalent binary complexes underwent ligation with different kinetics, presumably reflecting a dependence on DNA sequences flanking the individual topoisomerase I cleavage sites. Individual camptothecin derivatives also exhibited a spectrum of inhibitory potentials in blocking the topoisomerase I-mediated rearrangement of branched, nicked, and gapped DNA duplex substrates; in some cases the potencies of inhibition observed in these assays for individual camptothecin analogues were quite different than those determined for stabilization of the unmodified DNA-topoisomerase I binary complex.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Heteroduplexes,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9399-408
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9649322-Camptothecin,
pubmed-meshheading:9649322-DNA,
pubmed-meshheading:9649322-DNA Ligases,
pubmed-meshheading:9649322-DNA Topoisomerases, Type I,
pubmed-meshheading:9649322-Hydrolysis,
pubmed-meshheading:9649322-Nucleic Acid Heteroduplexes,
pubmed-meshheading:9649322-Sodium Chloride,
pubmed-meshheading:9649322-Substrate Specificity,
pubmed-meshheading:9649322-Topoisomerase I Inhibitors
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pubmed:year |
1998
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pubmed:articleTitle |
Differential effects of camptothecin derivatives on topoisomerase I-mediated DNA structure modification.
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pubmed:affiliation |
Department of Chemistry, University of Virginia, Charlottesville 22901, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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