Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH.
Identifieur interne : 002191 ( PubMed/Curation ); précédent : 002190; suivant : 002192Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH.
Auteurs : Sergey Antsypovich [États-Unis] ; Danaè Quirk-Dorr ; Crystal Pitts ; Natalia TretyakovaSource :
- Chemical research in toxicology [ 0893-228X ] ; 2007.
Descripteurs français
- KwdFr :
- Adduits à l'ADN (), Adduits à l'ADN (métabolisme), Adénosine (), Adénosine (analogues et dérivés), Chromatographie en phase liquide à haute performance, Composés époxy (), Concentration en ions d'hydrogène, Désoxyadénosine (), Spectrométrie de masse ESI, Spectroscopie par résonance magnétique, Structure moléculaire.
- MESH :
- analogues et dérivés : Adénosine.
- métabolisme : Adduits à l'ADN.
- Adduits à l'ADN, Adénosine, Chromatographie en phase liquide à haute performance, Composés époxy, Concentration en ions d'hydrogène, Désoxyadénosine, Spectrométrie de masse ESI, Spectroscopie par résonance magnétique, Structure moléculaire.
English descriptors
- KwdEn :
- Adenosine (analogs & derivatives), Adenosine (chemistry), Chromatography, High Pressure Liquid, DNA Adducts (chemistry), DNA Adducts (metabolism), Deoxyadenosines (chemistry), Epoxy Compounds (chemistry), Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, Molecular Structure, Spectrometry, Mass, Electrospray Ionization.
- MESH :
- chemical , analogs & derivatives : Adenosine.
- chemical , chemistry : Adenosine, DNA Adducts, Deoxyadenosines, Epoxy Compounds.
- chemical , metabolism : DNA Adducts.
- Chromatography, High Pressure Liquid, Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, Molecular Structure, Spectrometry, Mass, Electrospray Ionization.
Abstract
1,2,3,4-Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene, a high volume industrial chemical classified as a human and animal carcinogen. DEB is a bifunctional alkylating agent that exhibits both mutagenic and cytotoxic activity, presumably a result of its ability to form bifunctional DNA adducts. Initial reactions of DEB with DNA produce 2-hydroxy-3,4-epoxybut-1-yl (HEB) lesions at guanine and adenine nucleobases. The epoxy group of the monoadduct is inherently reactive and can then undergo further reactions, for example, hydrolysis to the corresponding 2,3,4-trihydroxybutyl adducts and/or second alkylation to yield 2,3-butanediol cross-links. In the present work, synthetic DNA 16-mers containing structurally defined racemic N6-(2-hydroxy-3,4-epoxybut-1-yl)-2'-deoxyadenosine (N6-HEB-dA) adducts (5'-AATTATGTXACGGTAG-3', where X = N6-HEB-dA) were prepared by coupling 6-chloropurine-containing oligodeoxynucleotides with 1-amino-2-hydroxy-3,4-epoxybutane. The latter was generated in situ from the corresponding Fmoc-protected amino epoxide. The N6-HEB-dA-containing DNA oligomer was isolated by reverse-phase HPLC, and the presence of N6-HEB-dA in its structure was confirmed by molecular weight determination and by HPLC-UV-ESI+-MS/MS analyses of enzymatic digests. An independently prepared N6-HEB-dA nucleoside served as an authentic standard. The fate of N6-HEB-dA within DNA at physiological conditions in the presence of various nucleophiles (e.g., cysteine, dG, and the complementary DNA strand) was investigated. Under all conditions tested, N6-HEB-dA rapidly cyclized to produce previously unidentified exocyclic dA lesions (t1/2 < 2 h at physiological conditions). Only trace amounts of hydrolyzed and cross-linked products were detected, suggesting that the rate of cyclization was much greater than the rates of other reactions at the epoxide ring. These results indicate that DEB-induced alkylation of N6-adenine in DNA is unlikely to lead to DNA-DNA cross-linking but instead can result in the formation of exocyclic dA adducts.
DOI: 10.1021/tx060178k
PubMed: 17355152
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :002191
Links to Exploration step
pubmed:17355152Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH.</title>
<author><name sortKey="Antsypovich, Sergey" sort="Antsypovich, Sergey" uniqKey="Antsypovich S" first="Sergey" last="Antsypovich">Sergey Antsypovich</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quirk Dorr, Danae" sort="Quirk Dorr, Danae" uniqKey="Quirk Dorr D" first="Danaè" last="Quirk-Dorr">Danaè Quirk-Dorr</name>
</author>
<author><name sortKey="Pitts, Crystal" sort="Pitts, Crystal" uniqKey="Pitts C" first="Crystal" last="Pitts">Crystal Pitts</name>
</author>
<author><name sortKey="Tretyakova, Natalia" sort="Tretyakova, Natalia" uniqKey="Tretyakova N" first="Natalia" last="Tretyakova">Natalia Tretyakova</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2007">2007</date>
<idno type="RBID">pubmed:17355152</idno>
<idno type="pmid">17355152</idno>
<idno type="doi">10.1021/tx060178k</idno>
<idno type="wicri:Area/PubMed/Corpus">002191</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002191</idno>
<idno type="wicri:Area/PubMed/Curation">002191</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002191</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH.</title>
<author><name sortKey="Antsypovich, Sergey" sort="Antsypovich, Sergey" uniqKey="Antsypovich S" first="Sergey" last="Antsypovich">Sergey Antsypovich</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Quirk Dorr, Danae" sort="Quirk Dorr, Danae" uniqKey="Quirk Dorr D" first="Danaè" last="Quirk-Dorr">Danaè Quirk-Dorr</name>
</author>
<author><name sortKey="Pitts, Crystal" sort="Pitts, Crystal" uniqKey="Pitts C" first="Crystal" last="Pitts">Crystal Pitts</name>
</author>
<author><name sortKey="Tretyakova, Natalia" sort="Tretyakova, Natalia" uniqKey="Tretyakova N" first="Natalia" last="Tretyakova">Natalia Tretyakova</name>
</author>
</analytic>
<series><title level="j">Chemical research in toxicology</title>
<idno type="ISSN">0893-228X</idno>
<imprint><date when="2007" type="published">2007</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine (analogs & derivatives)</term>
<term>Adenosine (chemistry)</term>
<term>Chromatography, High Pressure Liquid</term>
<term>DNA Adducts (chemistry)</term>
<term>DNA Adducts (metabolism)</term>
<term>Deoxyadenosines (chemistry)</term>
<term>Epoxy Compounds (chemistry)</term>
<term>Hydrogen-Ion Concentration</term>
<term>Magnetic Resonance Spectroscopy</term>
<term>Molecular Structure</term>
<term>Spectrometry, Mass, Electrospray Ionization</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adduits à l'ADN ()</term>
<term>Adduits à l'ADN (métabolisme)</term>
<term>Adénosine ()</term>
<term>Adénosine (analogues et dérivés)</term>
<term>Chromatographie en phase liquide à haute performance</term>
<term>Composés époxy ()</term>
<term>Concentration en ions d'hydrogène</term>
<term>Désoxyadénosine ()</term>
<term>Spectrométrie de masse ESI</term>
<term>Spectroscopie par résonance magnétique</term>
<term>Structure moléculaire</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenosine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Adenosine</term>
<term>DNA Adducts</term>
<term>Deoxyadenosines</term>
<term>Epoxy Compounds</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA Adducts</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Adénosine</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Adduits à l'ADN</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Chromatography, High Pressure Liquid</term>
<term>Hydrogen-Ion Concentration</term>
<term>Magnetic Resonance Spectroscopy</term>
<term>Molecular Structure</term>
<term>Spectrometry, Mass, Electrospray Ionization</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adduits à l'ADN</term>
<term>Adénosine</term>
<term>Chromatographie en phase liquide à haute performance</term>
<term>Composés époxy</term>
<term>Concentration en ions d'hydrogène</term>
<term>Désoxyadénosine</term>
<term>Spectrométrie de masse ESI</term>
<term>Spectroscopie par résonance magnétique</term>
<term>Structure moléculaire</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">1,2,3,4-Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene, a high volume industrial chemical classified as a human and animal carcinogen. DEB is a bifunctional alkylating agent that exhibits both mutagenic and cytotoxic activity, presumably a result of its ability to form bifunctional DNA adducts. Initial reactions of DEB with DNA produce 2-hydroxy-3,4-epoxybut-1-yl (HEB) lesions at guanine and adenine nucleobases. The epoxy group of the monoadduct is inherently reactive and can then undergo further reactions, for example, hydrolysis to the corresponding 2,3,4-trihydroxybutyl adducts and/or second alkylation to yield 2,3-butanediol cross-links. In the present work, synthetic DNA 16-mers containing structurally defined racemic N6-(2-hydroxy-3,4-epoxybut-1-yl)-2'-deoxyadenosine (N6-HEB-dA) adducts (5'-AATTATGTXACGGTAG-3', where X = N6-HEB-dA) were prepared by coupling 6-chloropurine-containing oligodeoxynucleotides with 1-amino-2-hydroxy-3,4-epoxybutane. The latter was generated in situ from the corresponding Fmoc-protected amino epoxide. The N6-HEB-dA-containing DNA oligomer was isolated by reverse-phase HPLC, and the presence of N6-HEB-dA in its structure was confirmed by molecular weight determination and by HPLC-UV-ESI+-MS/MS analyses of enzymatic digests. An independently prepared N6-HEB-dA nucleoside served as an authentic standard. The fate of N6-HEB-dA within DNA at physiological conditions in the presence of various nucleophiles (e.g., cysteine, dG, and the complementary DNA strand) was investigated. Under all conditions tested, N6-HEB-dA rapidly cyclized to produce previously unidentified exocyclic dA lesions (t1/2 < 2 h at physiological conditions). Only trace amounts of hydrolyzed and cross-linked products were detected, suggesting that the rate of cyclization was much greater than the rates of other reactions at the epoxide ring. These results indicate that DEB-induced alkylation of N6-adenine in DNA is unlikely to lead to DNA-DNA cross-linking but instead can result in the formation of exocyclic dA adducts.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17355152</PMID>
<DateCompleted><Year>2007</Year>
<Month>08</Month>
<Day>09</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>10</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0893-228X</ISSN>
<JournalIssue CitedMedium="Print"><Volume>20</Volume>
<Issue>4</Issue>
<PubDate><Year>2007</Year>
<Month>Apr</Month>
</PubDate>
</JournalIssue>
<Title>Chemical research in toxicology</Title>
<ISOAbbreviation>Chem. Res. Toxicol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH.</ArticleTitle>
<Pagination><MedlinePgn>641-9</MedlinePgn>
</Pagination>
<Abstract><AbstractText>1,2,3,4-Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene, a high volume industrial chemical classified as a human and animal carcinogen. DEB is a bifunctional alkylating agent that exhibits both mutagenic and cytotoxic activity, presumably a result of its ability to form bifunctional DNA adducts. Initial reactions of DEB with DNA produce 2-hydroxy-3,4-epoxybut-1-yl (HEB) lesions at guanine and adenine nucleobases. The epoxy group of the monoadduct is inherently reactive and can then undergo further reactions, for example, hydrolysis to the corresponding 2,3,4-trihydroxybutyl adducts and/or second alkylation to yield 2,3-butanediol cross-links. In the present work, synthetic DNA 16-mers containing structurally defined racemic N6-(2-hydroxy-3,4-epoxybut-1-yl)-2'-deoxyadenosine (N6-HEB-dA) adducts (5'-AATTATGTXACGGTAG-3', where X = N6-HEB-dA) were prepared by coupling 6-chloropurine-containing oligodeoxynucleotides with 1-amino-2-hydroxy-3,4-epoxybutane. The latter was generated in situ from the corresponding Fmoc-protected amino epoxide. The N6-HEB-dA-containing DNA oligomer was isolated by reverse-phase HPLC, and the presence of N6-HEB-dA in its structure was confirmed by molecular weight determination and by HPLC-UV-ESI+-MS/MS analyses of enzymatic digests. An independently prepared N6-HEB-dA nucleoside served as an authentic standard. The fate of N6-HEB-dA within DNA at physiological conditions in the presence of various nucleophiles (e.g., cysteine, dG, and the complementary DNA strand) was investigated. Under all conditions tested, N6-HEB-dA rapidly cyclized to produce previously unidentified exocyclic dA lesions (t1/2 < 2 h at physiological conditions). Only trace amounts of hydrolyzed and cross-linked products were detected, suggesting that the rate of cyclization was much greater than the rates of other reactions at the epoxide ring. These results indicate that DEB-induced alkylation of N6-adenine in DNA is unlikely to lead to DNA-DNA cross-linking but instead can result in the formation of exocyclic dA adducts.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Antsypovich</LastName>
<ForeName>Sergey</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Quirk-Dorr</LastName>
<ForeName>Danaè</ForeName>
<Initials>D</Initials>
</Author>
<Author ValidYN="Y"><LastName>Pitts</LastName>
<ForeName>Crystal</ForeName>
<Initials>C</Initials>
</Author>
<Author ValidYN="Y"><LastName>Tretyakova</LastName>
<ForeName>Natalia</ForeName>
<Initials>N</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 9CA095039</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
<PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2007</Year>
<Month>03</Month>
<Day>14</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Chem Res Toxicol</MedlineTA>
<NlmUniqueID>8807448</NlmUniqueID>
<ISSNLinking>0893-228X</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018736">DNA Adducts</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D003839">Deoxyadenosines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004852">Epoxy Compounds</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C521702">N6-(2-hydroxy-3,4-epoxybut-1-yl)-2'-deoxyadenosine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>60OB65YNAB</RegistryNumber>
<NameOfSubstance UI="C007366">diepoxybutane</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>K72T3FS567</RegistryNumber>
<NameOfSubstance UI="D000241">Adenosine</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000241" MajorTopicYN="N">Adenosine</DescriptorName>
<QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002851" MajorTopicYN="N">Chromatography, High Pressure Liquid</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018736" MajorTopicYN="N">DNA Adducts</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003839" MajorTopicYN="N">Deoxyadenosines</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004852" MajorTopicYN="N">Epoxy Compounds</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006863" MajorTopicYN="N">Hydrogen-Ion Concentration</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009682" MajorTopicYN="N">Magnetic Resonance Spectroscopy</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015394" MajorTopicYN="N">Molecular Structure</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D021241" MajorTopicYN="N">Spectrometry, Mass, Electrospray Ionization</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2007</Year>
<Month>3</Month>
<Day>16</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2007</Year>
<Month>8</Month>
<Day>10</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2007</Year>
<Month>3</Month>
<Day>16</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">17355152</ArticleId>
<ArticleId IdType="doi">10.1021/tx060178k</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/PubMed/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002191 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd -nk 002191 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= PubMed |étape= Curation |type= RBID |clé= pubmed:17355152 |texte= Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i -Sk "pubmed:17355152" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd \ | NlmPubMed2Wicri -a MersV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |