An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites.
Identifieur interne : 002841 ( Ncbi/Checkpoint ); précédent : 002840; suivant : 002842An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites.
Auteurs : P. Verspieren [France] ; A W Cornelissen ; N T Thuong ; C. Hélène ; J J ToulméSource :
- Gene [ 0378-1119 ] ; 1987.
Descripteurs français
- KwdFr :
- MESH :
- croissance et développement : Trypanosoma brucei brucei.
- génétique : ARN messager, Oligodésoxyribonucléotides, Trypanosoma brucei brucei.
- pharmacologie : Acridines.
- ADN recombiné, Animaux, Biosynthèse des protéines, Exons.
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
Affiliations:
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Verspieren</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UA481, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UA481, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></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. 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Verspieren</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UA481, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UA481, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></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="KwdFr" xml:lang="fr"><term>ADN recombiné</term><term>ARN messager (génétique)</term><term>Acridines (pharmacologie)</term><term>Animaux</term><term>Biosynthèse des protéines</term><term>Exons</term><term>Oligodésoxyribonucléotides (génétique)</term><term>Trypanosoma brucei brucei (croissance et développement)</term><term>Trypanosoma brucei brucei (génétique)</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="croissance et développement" xml:lang="fr"><term>Trypanosoma brucei brucei</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" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>Oligodésoxyribonucléotides</term><term>Trypanosoma brucei brucei</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acridines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>DNA, Recombinant</term><term>Exons</term><term>Protein Biosynthesis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ADN recombiné</term><term>Animaux</term><term>Biosynthèse des protéines</term><term>Exons</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><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Cornelissen, A W" sort="Cornelissen, A W" uniqKey="Cornelissen A" first="A W" last="Cornelissen">A W Cornelissen</name><name sortKey="Helene, C" sort="Helene, C" uniqKey="Helene C" first="C" last="Hélène">C. Hélène</name><name sortKey="Thuong, N T" sort="Thuong, N T" uniqKey="Thuong N" first="N T" last="Thuong">N T Thuong</name><name sortKey="Toulme, J J" sort="Toulme, J J" uniqKey="Toulme J" first="J J" last="Toulmé">J J Toulmé</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Verspieren, P" sort="Verspieren, P" uniqKey="Verspieren P" first="P" last="Verspieren">P. Verspieren</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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