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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2001-12-3
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pubmed:abstractText |
Ecteinascidin 743 (Et 743), a natural product derived from a marine tunicate, is a potent antitumor agent presently in phase II clinical trials. Et 743 binds in the minor groove of DNA and alkylates N2 of guanine via a unique mechanism involving catalytic activation. The sequence selectivity of Et 743 is governed by different patterns of hydrogen-bonding to DNA, which results in differential reversibility of the covalent adducts. As determined by nuclear magnetic resonance spectroscopy, the preferred sequences 5'-PuGC and 5'-PyGG are stabilized by a hydrogen-bonding network, while the non-preferred sequences 5'-NG(A/T) are much less stabilized due to the lack of a key hydrogen bond to the GC base pair on the 3'-side of the alkylated guanine.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Dioxoles,
http://linkedlifedata.com/resource/pubmed/chemical/Endodeoxyribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydroisoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/endodeoxyribonuclease uvrABC,
http://linkedlifedata.com/resource/pubmed/chemical/trabectedin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1074-5521
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1033-49
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pubmed:dateRevised |
2008-11-29
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pubmed:meshHeading |
pubmed-meshheading:11731295-Animals,
pubmed-meshheading:11731295-Antineoplastic Agents, Alkylating,
pubmed-meshheading:11731295-Base Sequence,
pubmed-meshheading:11731295-Binding Sites,
pubmed-meshheading:11731295-CHO Cells,
pubmed-meshheading:11731295-Cell Survival,
pubmed-meshheading:11731295-Cricetinae,
pubmed-meshheading:11731295-DNA,
pubmed-meshheading:11731295-DNA Adducts,
pubmed-meshheading:11731295-DNA Repair,
pubmed-meshheading:11731295-Dioxoles,
pubmed-meshheading:11731295-Drug Delivery Systems,
pubmed-meshheading:11731295-Endodeoxyribonucleases,
pubmed-meshheading:11731295-Escherichia coli Proteins,
pubmed-meshheading:11731295-Gene Targeting,
pubmed-meshheading:11731295-Humans,
pubmed-meshheading:11731295-Isoquinolines,
pubmed-meshheading:11731295-Models, Molecular,
pubmed-meshheading:11731295-Molecular Sequence Data,
pubmed-meshheading:11731295-Mutagenesis, Insertional,
pubmed-meshheading:11731295-Tetrahydroisoquinolines
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pubmed:year |
2001
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pubmed:articleTitle |
The inefficiency of incisions of ecteinascidin 743-DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent.
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pubmed:affiliation |
Department of Chemistry and Biochemistry, The University of Texas at Autin, 78712, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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