Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine-Phosphoramidite Method.
Identifieur interne : 000E94 ( PubMed/Checkpoint ); précédent : 000E93; suivant : 000E95Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine-Phosphoramidite Method.
Auteurs : Yohei Nukaga [Japon] ; Natsuhisa Oka [Japon] ; Takeshi Wada [Japon]Source :
- The Journal of organic chemistry [ 1520-6904 ] ; 2016.
Abstract
Stereocontrolled solid-phase synthesis of phosphate/phosphorothioate chimeric oligodeoxyribonucleotides (PO/PS-ODNs) was achieved by integrating the conventional phosphoramidite method into a previously developed oxazaphospholidine method for the stereocontrolled synthesis of P-chiral oligonucleotides. P-Stereodefined PO/PS-ODNs with mixed sequences (up to 12-mers) were obtained in good yields and high stereoselectivities by reacting different combinations of monomers (conventional phosphoramidites/diastereopure nucleoside 3'-O-oxazaphospholidines), activators (ETT/CMPT), capping reagents (Pac2O/CF3COIm), and oxidizing/sulfurizing reagents (TBHP/POS) on an automated synthesizer. A thermal denaturation study examined the resultant diastereopure PO/PS-ODN 12-mers with three consecutive (Rp)- or (Sp)-PS-linkages at the internal or terminal regions of the molecules. We found that (Rp)-PO/PS-ODNs can only moderately destabilize duplexes with complementary oligoribonucleotides (ORNs) compared with their unmodified ODN counterparts (ΔTm = -0.4 °C per modification). In contrast, (Sp)-PO/PS-ODNs have larger destabilizing effects (ΔTm = -1.2 to -0.8 °C per modification). Although smaller destabilizing effects were observed when the (Sp)-PS-linkages were incorporated into the terminal regions of the molecule, there was a weaker correlation between the location of an incorporated (Rp)-PS-linkage and its destabilizing effect.
DOI: 10.1021/acs.joc.5b02793
PubMed: 26939010
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:26939010Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine-Phosphoramidite Method.</title>
<author><name sortKey="Nukaga, Yohei" sort="Nukaga, Yohei" uniqKey="Nukaga Y" first="Yohei" last="Nukaga">Yohei Nukaga</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510</wicri:regionArea>
<wicri:noRegion>Chiba 278-8510</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Oka, Natsuhisa" sort="Oka, Natsuhisa" uniqKey="Oka N" first="Natsuhisa" last="Oka">Natsuhisa Oka</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu 501-1193, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu 501-1193</wicri:regionArea>
<wicri:noRegion>Gifu 501-1193</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wada, Takeshi" sort="Wada, Takeshi" uniqKey="Wada T" first="Takeshi" last="Wada">Takeshi Wada</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510</wicri:regionArea>
<wicri:noRegion>Chiba 278-8510</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2016">2016</date>
<idno type="RBID">pubmed:26939010</idno>
<idno type="pmid">26939010</idno>
<idno type="doi">10.1021/acs.joc.5b02793</idno>
<idno type="wicri:Area/PubMed/Corpus">001225</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001225</idno>
<idno type="wicri:Area/PubMed/Curation">001225</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001225</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000E94</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E94</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine-Phosphoramidite Method.</title>
<author><name sortKey="Nukaga, Yohei" sort="Nukaga, Yohei" uniqKey="Nukaga Y" first="Yohei" last="Nukaga">Yohei Nukaga</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510</wicri:regionArea>
<wicri:noRegion>Chiba 278-8510</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Oka, Natsuhisa" sort="Oka, Natsuhisa" uniqKey="Oka N" first="Natsuhisa" last="Oka">Natsuhisa Oka</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu 501-1193, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu 501-1193</wicri:regionArea>
<wicri:noRegion>Gifu 501-1193</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wada, Takeshi" sort="Wada, Takeshi" uniqKey="Wada T" first="Takeshi" last="Wada">Takeshi Wada</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510</wicri:regionArea>
<wicri:noRegion>Chiba 278-8510</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of organic chemistry</title>
<idno type="eISSN">1520-6904</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Stereocontrolled solid-phase synthesis of phosphate/phosphorothioate chimeric oligodeoxyribonucleotides (PO/PS-ODNs) was achieved by integrating the conventional phosphoramidite method into a previously developed oxazaphospholidine method for the stereocontrolled synthesis of P-chiral oligonucleotides. P-Stereodefined PO/PS-ODNs with mixed sequences (up to 12-mers) were obtained in good yields and high stereoselectivities by reacting different combinations of monomers (conventional phosphoramidites/diastereopure nucleoside 3'-O-oxazaphospholidines), activators (ETT/CMPT), capping reagents (Pac2O/CF3COIm), and oxidizing/sulfurizing reagents (TBHP/POS) on an automated synthesizer. A thermal denaturation study examined the resultant diastereopure PO/PS-ODN 12-mers with three consecutive (Rp)- or (Sp)-PS-linkages at the internal or terminal regions of the molecules. We found that (Rp)-PO/PS-ODNs can only moderately destabilize duplexes with complementary oligoribonucleotides (ORNs) compared with their unmodified ODN counterparts (ΔTm = -0.4 °C per modification). In contrast, (Sp)-PO/PS-ODNs have larger destabilizing effects (ΔTm = -1.2 to -0.8 °C per modification). Although smaller destabilizing effects were observed when the (Sp)-PS-linkages were incorporated into the terminal regions of the molecule, there was a weaker correlation between the location of an incorporated (Rp)-PS-linkage and its destabilizing effect. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">26939010</PMID>
<DateCompleted><Year>2016</Year>
<Month>08</Month>
<Day>18</Day>
</DateCompleted>
<DateRevised><Year>2016</Year>
<Month>04</Month>
<Day>01</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-6904</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>81</Volume>
<Issue>7</Issue>
<PubDate><Year>2016</Year>
<Month>Apr</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of organic chemistry</Title>
<ISOAbbreviation>J. Org. Chem.</ISOAbbreviation>
</Journal>
<ArticleTitle>Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine-Phosphoramidite Method.</ArticleTitle>
<Pagination><MedlinePgn>2753-62</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1021/acs.joc.5b02793</ELocationID>
<Abstract><AbstractText>Stereocontrolled solid-phase synthesis of phosphate/phosphorothioate chimeric oligodeoxyribonucleotides (PO/PS-ODNs) was achieved by integrating the conventional phosphoramidite method into a previously developed oxazaphospholidine method for the stereocontrolled synthesis of P-chiral oligonucleotides. P-Stereodefined PO/PS-ODNs with mixed sequences (up to 12-mers) were obtained in good yields and high stereoselectivities by reacting different combinations of monomers (conventional phosphoramidites/diastereopure nucleoside 3'-O-oxazaphospholidines), activators (ETT/CMPT), capping reagents (Pac2O/CF3COIm), and oxidizing/sulfurizing reagents (TBHP/POS) on an automated synthesizer. A thermal denaturation study examined the resultant diastereopure PO/PS-ODN 12-mers with three consecutive (Rp)- or (Sp)-PS-linkages at the internal or terminal regions of the molecules. We found that (Rp)-PO/PS-ODNs can only moderately destabilize duplexes with complementary oligoribonucleotides (ORNs) compared with their unmodified ODN counterparts (ΔTm = -0.4 °C per modification). In contrast, (Sp)-PO/PS-ODNs have larger destabilizing effects (ΔTm = -1.2 to -0.8 °C per modification). Although smaller destabilizing effects were observed when the (Sp)-PS-linkages were incorporated into the terminal regions of the molecule, there was a weaker correlation between the location of an incorporated (Rp)-PS-linkage and its destabilizing effect. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nukaga</LastName>
<ForeName>Yohei</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oka</LastName>
<ForeName>Natsuhisa</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu 501-1193, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wada</LastName>
<ForeName>Takeshi</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>03</Month>
<Day>14</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Org Chem</MedlineTA>
<NlmUniqueID>2985193R</NlmUniqueID>
<ISSNLinking>0022-3263</ISSNLinking>
</MedlineJournalInfo>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>3</Month>
<Day>4</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>3</Month>
<Day>5</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2016</Year>
<Month>3</Month>
<Day>5</Day>
<Hour>6</Hour>
<Minute>1</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">26939010</ArticleId>
<ArticleId IdType="doi">10.1021/acs.joc.5b02793</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Japon</li>
</country>
</list>
<tree><country name="Japon"><noRegion><name sortKey="Nukaga, Yohei" sort="Nukaga, Yohei" uniqKey="Nukaga Y" first="Yohei" last="Nukaga">Yohei Nukaga</name>
</noRegion>
<name sortKey="Oka, Natsuhisa" sort="Oka, Natsuhisa" uniqKey="Oka N" first="Natsuhisa" last="Oka">Natsuhisa Oka</name>
<name sortKey="Wada, Takeshi" sort="Wada, Takeshi" uniqKey="Wada T" first="Takeshi" last="Wada">Takeshi Wada</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000E94 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 000E94 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= PubMed |étape= Checkpoint |type= RBID |clé= pubmed:26939010 |texte= Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine-Phosphoramidite Method. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:26939010" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a MersV1
This area was generated with Dilib version V0.6.33. |