Structure-activity relationships of cytotoxic cholesterol-modified DNA duplexes.
Identifieur interne : 002876 ( Ncbi/Merge ); précédent : 002875; suivant : 002877Structure-activity relationships of cytotoxic cholesterol-modified DNA duplexes.
Auteurs : M W Reed [États-Unis] ; E A Lukhtanov ; V V Gorn ; D D Lucas ; J H Zhou ; S B Pai ; Y C Cheng ; R B MeyerSource :
- Journal of medicinal chemistry [ 0022-2623 ] ; 1995.
Descripteurs français
- KwdFr :
- ADN (), ADN (pharmacologie), Antinéoplasiques (), Antinéoplasiques (pharmacologie), Antinéoplasiques (synthèse chimique), Carcinome hépatocellulaire, Cellules cancéreuses en culture, Cholestérol (), Cholestérol (analogues et dérivés), Cholestérol (pharmacologie), Clones cellulaires, Données de séquences moléculaires, Relation structure-activité, Spectroscopie par résonance magnétique, Séquence nucléotidique, Tests de criblage d'agents antitumoraux.
- MESH :
- analogues et dérivés : Cholestérol.
- pharmacologie : ADN, Antinéoplasiques, Cholestérol.
- synthèse chimique : Antinéoplasiques.
- ADN, Antinéoplasiques, Carcinome hépatocellulaire, Cellules cancéreuses en culture, Cholestérol, Clones cellulaires, Données de séquences moléculaires, Relation structure-activité, Spectroscopie par résonance magnétique, Séquence nucléotidique, Tests de criblage d'agents antitumoraux.
English descriptors
- KwdEn :
- Antineoplastic Agents (chemical synthesis), Antineoplastic Agents (chemistry), Antineoplastic Agents (pharmacology), Base Sequence, Carcinoma, Hepatocellular, Cholesterol (analogs & derivatives), Cholesterol (chemistry), Cholesterol (pharmacology), Clone Cells, DNA (chemistry), DNA (pharmacology), Drug Screening Assays, Antitumor, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Structure-Activity Relationship, Tumor Cells, Cultured.
- MESH :
- chemical , analogs & derivatives : Cholesterol.
- chemical , chemical synthesis : Antineoplastic Agents.
- chemical , chemistry : Antineoplastic Agents, Cholesterol, DNA.
- chemical , pharmacology : Antineoplastic Agents, Cholesterol, DNA.
- Base Sequence, Carcinoma, Hepatocellular, Clone Cells, Drug Screening Assays, Antitumor, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Structure-Activity Relationship, Tumor Cells, Cultured.
Abstract
Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mumol scale and simplified purification.
DOI: 10.1021/jm00022a025
PubMed: 7473587
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- to stream PubMed, to step Corpus: 002797
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pubmed:7473587Le document en format XML
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(chemistry)</term><term>Antineoplastic Agents (pharmacology)</term><term>Base Sequence</term><term>Carcinoma, Hepatocellular</term><term>Cholesterol (analogs & derivatives)</term><term>Cholesterol (chemistry)</term><term>Cholesterol (pharmacology)</term><term>Clone Cells</term><term>DNA (chemistry)</term><term>DNA (pharmacology)</term><term>Drug Screening Assays, Antitumor</term><term>Magnetic Resonance Spectroscopy</term><term>Molecular Sequence Data</term><term>Structure-Activity Relationship</term><term>Tumor Cells, Cultured</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN ()</term><term>ADN (pharmacologie)</term><term>Antinéoplasiques ()</term><term>Antinéoplasiques (pharmacologie)</term><term>Antinéoplasiques (synthèse chimique)</term><term>Carcinome hépatocellulaire</term><term>Cellules cancéreuses en culture</term><term>Cholestérol ()</term><term>Cholestérol (analogues et dérivés)</term><term>Cholestérol (pharmacologie)</term><term>Clones cellulaires</term><term>Données de séquences moléculaires</term><term>Relation structure-activité</term><term>Spectroscopie par résonance magnétique</term><term>Séquence nucléotidique</term><term>Tests de criblage d'agents antitumoraux</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Cholesterol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antineoplastic Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antineoplastic Agents</term><term>Cholesterol</term><term>DNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Cholesterol</term><term>DNA</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Cholestérol</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" 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antitumoraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mumol scale and simplified purification.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">7473587</PMID><DateCompleted><Year>1995</Year><Month>12</Month><Day>26</Day></DateCompleted><DateRevised><Year>2019</Year><Month>07</Month><Day>09</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-2623</ISSN><JournalIssue CitedMedium="Print"><Volume>38</Volume><Issue>22</Issue><PubDate><Year>1995</Year><Month>Oct</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of medicinal chemistry</Title><ISOAbbreviation>J. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Structure-activity relationships of cytotoxic cholesterol-modified DNA duplexes.</ArticleTitle><Pagination><MedlinePgn>4587-96</MedlinePgn></Pagination><Abstract><AbstractText>Short DNA duplexes with cholesterol linked at the 3'-terminus of each strand have unique, selective cytotoxic properties. The structural requirements for biological activity were explored through chemical synthesis of analogs and testing in cultured hepatoma cells. Effects of modifications to the sequence, backbone, 3'-sterol, 3'-linker, and 5'-terminus were evaluated. Self-complementary 3'-modified oligodeoxynucleotide (ODN) 10-mers were prepared from solid supports bearing the modification and linker of interest. Any changes to the normal phosphodiester backbone were poorly tolerated. The presence of cholesterol or a closely related sterol was an absolute requirement for activity. The length and position of attachment of the linker to cholesterol was important, with longer linkers showing reduced activity. Large, lipophilic groups at the 5'-terminus gave reduced cytotoxicity and poor solubility properties. The short length and unique structure of these ODNs allowed efficient automated synthesis on a 400 mumol scale and simplified purification.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Reed</LastName><ForeName>M W</ForeName><Initials>MW</Initials><AffiliationInfo><Affiliation>MicroProbe Corporation, Bothell, Washington 98021, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lukhtanov</LastName><ForeName>E A</ForeName><Initials>EA</Initials></Author><Author ValidYN="Y"><LastName>Gorn</LastName><ForeName>V V</ForeName><Initials>VV</Initials></Author><Author ValidYN="Y"><LastName>Lucas</LastName><ForeName>D D</ForeName><Initials>DD</Initials></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>J H</ForeName><Initials>JH</Initials></Author><Author ValidYN="Y"><LastName>Pai</LastName><ForeName>S B</ForeName><Initials>SB</Initials></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Y C</ForeName><Initials>YC</Initials></Author><Author ValidYN="Y"><LastName>Meyer</LastName><ForeName>R B</ForeName><Initials>RB</Initials><Suffix>Jr</Suffix></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>AI29277</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA09085</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA44358</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Med 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MajorTopicYN="N">Magnetic Resonance Spectroscopy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1995</Year><Month>10</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1995</Year><Month>10</Month><Day>27</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1995</Year><Month>10</Month><Day>27</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">7473587</ArticleId><ArticleId IdType="doi">10.1021/jm00022a025</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Cheng, Y C" sort="Cheng, Y C" uniqKey="Cheng Y" first="Y C" last="Cheng">Y C Cheng</name><name sortKey="Gorn, V V" sort="Gorn, V V" uniqKey="Gorn V" first="V V" last="Gorn">V V Gorn</name><name sortKey="Lucas, D D" sort="Lucas, D D" uniqKey="Lucas D" first="D D" last="Lucas">D D Lucas</name><name sortKey="Lukhtanov, E A" sort="Lukhtanov, E A" uniqKey="Lukhtanov E" first="E A" last="Lukhtanov">E A Lukhtanov</name><name sortKey="Meyer, R B" sort="Meyer, R B" uniqKey="Meyer R" first="R B" last="Meyer">R B Meyer</name><name sortKey="Pai, S B" sort="Pai, S B" uniqKey="Pai S" first="S B" last="Pai">S B Pai</name><name sortKey="Zhou, J H" sort="Zhou, J H" uniqKey="Zhou J" first="J H" last="Zhou">J H Zhou</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Reed, M W" sort="Reed, M W" uniqKey="Reed M" first="M W" last="Reed">M W Reed</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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