rdf:type |
|
lifeskim:mentions |
umls-concept:C0002074,
umls-concept:C0010843,
umls-concept:C0012854,
umls-concept:C0018321,
umls-concept:C0020944,
umls-concept:C0054919,
umls-concept:C0178499,
umls-concept:C0205198,
umls-concept:C0209891,
umls-concept:C0332120,
umls-concept:C1511539,
umls-concept:C1522538,
umls-concept:C1626935
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pubmed:issue |
6
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pubmed:dateCreated |
1994-4-4
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pubmed:abstractText |
Bizelesin, an intrahelical DNA-DNA interstrand cross-linker related to (+)-CC-1065, has been shown to alkylate DNA through guanine in restriction enzyme sequences in which there is a suitably positioned adenine contained in a highly reactive monoalkylation sequence on the opposite strand. Oligomers containing the sequence 5'-TTTTTN*, in which "N" was either G, C, or T, were synthesized to evaluate the cross-linking potential of bizelesin at nonadenine bases. Kinetic analysis of monoalkylation and cross-linking events demonstrates that it is the reaction at "N" (guanine or cytosine) that results in the cross-link which is the slow step. On the basis of this analysis and the normal unreactivity of guanine and cytosine to alkylation by the cyclopropapyrroloindole alkylating moiety of (+)-CC-1065, we propose that the molecular mechanism for this type of cross-linking reaction most likely involves a covalent immobilization of the second alkylating arm, resulting in a "proximity-driven" reaction.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkylating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/CC 1065,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Cytosine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Leucomycins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Urea,
http://linkedlifedata.com/resource/pubmed/chemical/bizelesin
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pubmed:status |
MEDLINE
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pubmed:issn |
0893-228X
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
889-94
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8117929-Alkylating Agents,
pubmed-meshheading:8117929-Alkylation,
pubmed-meshheading:8117929-Antibiotics, Antineoplastic,
pubmed-meshheading:8117929-Base Composition,
pubmed-meshheading:8117929-Base Sequence,
pubmed-meshheading:8117929-Cross-Linking Reagents,
pubmed-meshheading:8117929-Cytosine,
pubmed-meshheading:8117929-DNA,
pubmed-meshheading:8117929-Guanine,
pubmed-meshheading:8117929-Indoles,
pubmed-meshheading:8117929-Kinetics,
pubmed-meshheading:8117929-Leucomycins,
pubmed-meshheading:8117929-Molecular Sequence Data,
pubmed-meshheading:8117929-Oligonucleotides,
pubmed-meshheading:8117929-Urea
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pubmed:articleTitle |
Alkylation of guanine and cytosine in DNA by bizelesin. Evidence for a covalent immobilization leading to a proximity-driven alkylation of normally unreactive bases by a (+)-CC-1065 cross-linking compound.
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pubmed:affiliation |
Drug Dynamics Institute, College of Pharmacy, University of Texas at Austin 78712.
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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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