An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites.
Identifieur interne : 002A78 ( PubMed/Corpus ); précédent : 002A77; suivant : 002A79An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites.
Auteurs : P. Verspieren ; A W Cornelissen ; N T Thuong ; C. Hélène ; J J ToulméSource :
- Gene [ 0378-1119 ] ; 1987.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Oligodeoxyribonucleotides, RNA, Messenger.
- chemical , pharmacology : Acridines.
- genetics : Trypanosoma brucei brucei.
- growth & development : Trypanosoma brucei brucei.
- Animals, DNA, Recombinant, Exons, Protein Biosynthesis.
Abstract
Anti-messenger oligodeoxynucleotides covalently linked to an intercalating agent were tested for their ability to inhibit translation of Trypanosoma brucei mRNAs in a cell-free system. The sequence of these oligodeoxynucleotides was complementary to part of the 35-nucleotide (nt) sequence which is present at the 5' end of all trypanosome mRNAs (the so-called mini-exon sequence). In a rabbit reticulocyte lysate, a nonadeoxynucleotide linked to an acridine derivative, specifically inhibited protein synthesis from T. brucei mRNAs much more efficiently than unmodified oligodeoxynucleotides of similar length. These oligodeoxynucleotides were tested on cultured trypanosomes. The acridine-linked nonadeoxynucleotide had a lethal effect on the parasites. No effect was observed with the homologous unmodified 9-mer nor with those 9-mers linked to the acridine derivative which were not complementary to the mini-exon sequence. These effects are probably a result of hybrid formation between the anti-messenger and mini-exon sequence. Trypanocidal activity of the acridine-modified nonadeoxynucleotide is most likely due to (i) increased affinity for its target, (ii) improved resistance to 3' exonucleases, and (iii) promoted membrane penetration of living parasites.
DOI: 10.1016/0378-1119(87)90194-6
PubMed: 3446576
Links to Exploration step
pubmed:3446576Le document en format XML
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Hélène</name></author><author><name sortKey="Toulme, J J" sort="Toulme, J J" uniqKey="Toulme J" first="J J" last="Toulmé">J J Toulmé</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1987">1987</date><idno type="RBID">pubmed:3446576</idno><idno type="pmid">3446576</idno><idno type="doi">10.1016/0378-1119(87)90194-6</idno><idno type="wicri:Area/PubMed/Corpus">002A78</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002A78</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites.</title><author><name sortKey="Verspieren, P" sort="Verspieren, P" uniqKey="Verspieren P" first="P" last="Verspieren">P. Verspieren</name><affiliation><nlm:affiliation>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UA481, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cornelissen, A W" sort="Cornelissen, A W" uniqKey="Cornelissen A" first="A W" last="Cornelissen">A W Cornelissen</name></author><author><name sortKey="Thuong, N T" sort="Thuong, N T" uniqKey="Thuong N" first="N T" last="Thuong">N T Thuong</name></author><author><name sortKey="Helene, C" sort="Helene, C" uniqKey="Helene C" first="C" last="Hélène">C. Hélène</name></author><author><name sortKey="Toulme, J J" sort="Toulme, J J" uniqKey="Toulme J" first="J J" last="Toulmé">J J Toulmé</name></author></analytic><series><title level="j">Gene</title><idno type="ISSN">0378-1119</idno><imprint><date when="1987" type="published">1987</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acridines (pharmacology)</term><term>Animals</term><term>DNA, Recombinant</term><term>Exons</term><term>Oligodeoxyribonucleotides (genetics)</term><term>Protein Biosynthesis</term><term>RNA, Messenger (genetics)</term><term>Trypanosoma brucei brucei (genetics)</term><term>Trypanosoma brucei brucei (growth & development)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Oligodeoxyribonucleotides</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Acridines</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Trypanosoma brucei brucei</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Trypanosoma brucei brucei</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>DNA, Recombinant</term><term>Exons</term><term>Protein Biosynthesis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Anti-messenger oligodeoxynucleotides covalently linked to an intercalating agent were tested for their ability to inhibit translation of Trypanosoma brucei mRNAs in a cell-free system. The sequence of these oligodeoxynucleotides was complementary to part of the 35-nucleotide (nt) sequence which is present at the 5' end of all trypanosome mRNAs (the so-called mini-exon sequence). In a rabbit reticulocyte lysate, a nonadeoxynucleotide linked to an acridine derivative, specifically inhibited protein synthesis from T. brucei mRNAs much more efficiently than unmodified oligodeoxynucleotides of similar length. These oligodeoxynucleotides were tested on cultured trypanosomes. The acridine-linked nonadeoxynucleotide had a lethal effect on the parasites. No effect was observed with the homologous unmodified 9-mer nor with those 9-mers linked to the acridine derivative which were not complementary to the mini-exon sequence. These effects are probably a result of hybrid formation between the anti-messenger and mini-exon sequence. Trypanocidal activity of the acridine-modified nonadeoxynucleotide is most likely due to (i) increased affinity for its target, (ii) improved resistance to 3' exonucleases, and (iii) promoted membrane penetration of living parasites.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">3446576</PMID><DateCompleted><Year>1988</Year><Month>05</Month><Day>24</Day></DateCompleted><DateRevised><Year>2019</Year><Month>07</Month><Day>07</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0378-1119</ISSN><JournalIssue CitedMedium="Print"><Volume>61</Volume><Issue>3</Issue><PubDate><Year>1987</Year></PubDate></JournalIssue><Title>Gene</Title><ISOAbbreviation>Gene</ISOAbbreviation></Journal><ArticleTitle>An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites.</ArticleTitle><Pagination><MedlinePgn>307-15</MedlinePgn></Pagination><Abstract><AbstractText>Anti-messenger oligodeoxynucleotides covalently linked to an intercalating agent were tested for their ability to inhibit translation of Trypanosoma brucei mRNAs in a cell-free system. The sequence of these oligodeoxynucleotides was complementary to part of the 35-nucleotide (nt) sequence which is present at the 5' end of all trypanosome mRNAs (the so-called mini-exon sequence). In a rabbit reticulocyte lysate, a nonadeoxynucleotide linked to an acridine derivative, specifically inhibited protein synthesis from T. brucei mRNAs much more efficiently than unmodified oligodeoxynucleotides of similar length. These oligodeoxynucleotides were tested on cultured trypanosomes. The acridine-linked nonadeoxynucleotide had a lethal effect on the parasites. No effect was observed with the homologous unmodified 9-mer nor with those 9-mers linked to the acridine derivative which were not complementary to the mini-exon sequence. These effects are probably a result of hybrid formation between the anti-messenger and mini-exon sequence. Trypanocidal activity of the acridine-modified nonadeoxynucleotide is most likely due to (i) increased affinity for its target, (ii) improved resistance to 3' exonucleases, and (iii) promoted membrane penetration of living parasites.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Verspieren</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UA481, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cornelissen</LastName><ForeName>A W</ForeName><Initials>AW</Initials></Author><Author ValidYN="Y"><LastName>Thuong</LastName><ForeName>N T</ForeName><Initials>NT</Initials></Author><Author ValidYN="Y"><LastName>Hélène</LastName><ForeName>C</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Toulmé</LastName><ForeName>J J</ForeName><Initials>JJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Gene</MedlineTA><NlmUniqueID>7706761</NlmUniqueID><ISSNLinking>0378-1119</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000166">Acridines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004274">DNA, Recombinant</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009838">Oligodeoxyribonucleotides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000166" MajorTopicYN="N">Acridines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004274" MajorTopicYN="Y">DNA, Recombinant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005091" MajorTopicYN="N">Exons</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009838" MajorTopicYN="N">Oligodeoxyribonucleotides</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014176" MajorTopicYN="N">Protein Biosynthesis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014346" MajorTopicYN="N">Trypanosoma brucei brucei</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1987</Year><Month>1</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1987</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1987</Year><Month>1</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">3446576</ArticleId><ArticleId IdType="pii">0378-1119(87)90194-6</ArticleId><ArticleId IdType="doi">10.1016/0378-1119(87)90194-6</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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