Site-specific interaction of intercalating drugs with a branched DNA molecule.
Identifieur interne : 004A95 ( Main/Exploration ); précédent : 004A94; suivant : 004A96Site-specific interaction of intercalating drugs with a branched DNA molecule.
Auteurs : Q. Guo [États-Unis] ; N C Seeman ; N R KallenbachSource :
- Biochemistry [ 0006-2960 ] ; 1989.
Descripteurs français
- KwdFr :
- MESH :
- analogues et dérivés : Acide édétique.
- ADN, Agents chélateurs du fer, Conformation d'acide nucléique, Hydroxydes, Modèles moléculaires, Radical hydroxyle, Radicaux libres.
English descriptors
- KwdEn :
- MESH :
- chemical , analogs & derivatives : Edetic Acid.
- chemical : DNA, Free Radicals, Hydroxides, Hydroxyl Radical, Iron Chelating Agents.
- Models, Molecular, Nucleic Acid Conformation.
Abstract
The interaction of a stable branched DNA molecule with an intercalative drug is probed by hydroxyl radical scission. Methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II)], consisting of an intercalating ring system tethered to EDTA.Fe(II), produces the hydroxyl radicals by means of a Fenton reaction. The cleavage patterns of each labeled strand in a branched tetramer of four 16-mers are compared with those of the same strands in unbranched duplex controls. Strong differences between the profiles corresponding to scission of branched and duplex DNA molecules are seen in each of the strands at low MPE/DNA ratios. A specific site in the branched structure interacts preferentially with the drug, while other regions of the molecule are protected from cleavage. At 4 degrees C, cutting at strand positions demarcating the site of enhanced affinity is observed to be 60-100% more efficient than at the corresponding sequence positions in the control duplex DNA molecules; the degree of protection is comparable. Cleavage in the vicinity of the preferred site occurs at residues flanking the branch point. The reactive Fe(II) group appears to be centered within two residues of the branch point, and the site of preferential intercalation may be between the two base pairs abutting the branch point in one of the two helical domains. The pattern of preferential cutting at this site is eliminated in the presence of excess propidium diiodide, another intercalative drug.
DOI: 10.1021/bi00432a001
PubMed: 2543439
Affiliations:
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Le document en format XML
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Guo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry, New York University, New York 10003.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Chemistry, New York University</wicri:cityArea></affiliation></author><author><name sortKey="Seeman, N C" sort="Seeman, N C" uniqKey="Seeman N" first="N C" last="Seeman">N C Seeman</name></author><author><name sortKey="Kallenbach, N R" sort="Kallenbach, N R" uniqKey="Kallenbach N" first="N R" last="Kallenbach">N R Kallenbach</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1989">1989</date><idno type="RBID">pubmed:2543439</idno><idno type="pmid">2543439</idno><idno type="doi">10.1021/bi00432a001</idno><idno type="wicri:Area/PubMed/Corpus">002A43</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002A43</idno><idno type="wicri:Area/PubMed/Curation">002A43</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002A43</idno><idno type="wicri:Area/PubMed/Checkpoint">002881</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002881</idno><idno type="wicri:Area/Ncbi/Merge">000F69</idno><idno type="wicri:Area/Ncbi/Curation">000F69</idno><idno type="wicri:Area/Ncbi/Checkpoint">000F69</idno><idno type="wicri:doubleKey">0006-2960:1989:Guo Q:site:specific:interaction</idno><idno type="wicri:Area/Main/Merge">004B73</idno><idno type="wicri:Area/Main/Curation">004A95</idno><idno type="wicri:Area/Main/Exploration">004A95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Site-specific interaction of intercalating drugs with a branched DNA molecule.</title><author><name sortKey="Guo, Q" sort="Guo, Q" uniqKey="Guo Q" first="Q" last="Guo">Q. Guo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry, New York University, New York 10003.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Chemistry, New York University</wicri:cityArea></affiliation></author><author><name sortKey="Seeman, N C" sort="Seeman, N C" uniqKey="Seeman N" first="N C" last="Seeman">N C Seeman</name></author><author><name sortKey="Kallenbach, N R" sort="Kallenbach, N R" uniqKey="Kallenbach N" first="N R" last="Kallenbach">N R Kallenbach</name></author></analytic><series><title level="j">Biochemistry</title><idno type="ISSN">0006-2960</idno><imprint><date when="1989" type="published">1989</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>DNA</term><term>Edetic Acid (analogs & derivatives)</term><term>Free Radicals</term><term>Hydroxides</term><term>Hydroxyl Radical</term><term>Iron Chelating Agents</term><term>Models, Molecular</term><term>Nucleic Acid Conformation</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN</term><term>Acide édétique (analogues et dérivés)</term><term>Agents chélateurs du fer</term><term>Conformation d'acide nucléique</term><term>Hydroxydes</term><term>Modèles moléculaires</term><term>Radical hydroxyle</term><term>Radicaux libres</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Edetic Acid</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>DNA</term><term>Free Radicals</term><term>Hydroxides</term><term>Hydroxyl Radical</term><term>Iron Chelating Agents</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Acide édétique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Models, Molecular</term><term>Nucleic Acid Conformation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ADN</term><term>Agents chélateurs du fer</term><term>Conformation d'acide nucléique</term><term>Hydroxydes</term><term>Modèles moléculaires</term><term>Radical hydroxyle</term><term>Radicaux libres</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The interaction of a stable branched DNA molecule with an intercalative drug is probed by hydroxyl radical scission. Methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II)], consisting of an intercalating ring system tethered to EDTA.Fe(II), produces the hydroxyl radicals by means of a Fenton reaction. The cleavage patterns of each labeled strand in a branched tetramer of four 16-mers are compared with those of the same strands in unbranched duplex controls. Strong differences between the profiles corresponding to scission of branched and duplex DNA molecules are seen in each of the strands at low MPE/DNA ratios. A specific site in the branched structure interacts preferentially with the drug, while other regions of the molecule are protected from cleavage. At 4 degrees C, cutting at strand positions demarcating the site of enhanced affinity is observed to be 60-100% more efficient than at the corresponding sequence positions in the control duplex DNA molecules; the degree of protection is comparable. Cleavage in the vicinity of the preferred site occurs at residues flanking the branch point. The reactive Fe(II) group appears to be centered within two residues of the branch point, and the site of preferential intercalation may be between the two base pairs abutting the branch point in one of the two helical domains. The pattern of preferential cutting at this site is eliminated in the presence of excess propidium diiodide, another intercalative drug.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><noCountry><name sortKey="Kallenbach, N R" sort="Kallenbach, N R" uniqKey="Kallenbach N" first="N R" last="Kallenbach">N R Kallenbach</name><name sortKey="Seeman, N C" sort="Seeman, N C" uniqKey="Seeman N" first="N C" last="Seeman">N C Seeman</name></noCountry><country name="États-Unis"><region name="État de New York"><name sortKey="Guo, Q" sort="Guo, Q" uniqKey="Guo Q" first="Q" last="Guo">Q. Guo</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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