Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNA(Leu(UUR)) and tRNA(Lys).
Identifieur interne : 001D19 ( Main/Exploration ); précédent : 001D18; suivant : 001D20Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNA(Leu(UUR)) and tRNA(Lys).
Auteurs : Grazyna Leszczynska [Pologne] ; Piotr Leonczak [Pologne] ; Karolina Wozniak [Pologne] ; Andrzej Malkiewicz [Pologne]Source :
- RNA (New York, N.Y.) [ 1469-9001 ] ; 2014.
Descripteurs français
- KwdFr :
- 4-Thiouridine (analogues et dérivés), 4-Thiouridine (synthèse chimique), ARN de transfert de la leucine (génétique), ARN de transfert de la lysine (génétique), Anticodon (génétique), Conformation d'acide nucléique, Humains, Mitochondries (génétique), Mutation (génétique), Oligoribonucléotides (génétique).
- MESH :
- analogues et dérivés : 4-Thiouridine.
- génétique : ARN de transfert de la leucine, ARN de transfert de la lysine, Anticodon, Mitochondries, Mutation, Oligoribonucléotides.
- synthèse chimique : 4-Thiouridine.
- Conformation d'acide nucléique, Humains.
English descriptors
- KwdEn :
- MESH :
- chemical , analogs & derivatives : Thiouridine.
- chemical , chemical synthesis : Thiouridine.
- chemical , genetics : Anticodon, Oligoribonucleotides, RNA, Transfer, Leu, RNA, Transfer, Lys.
- genetics : Mitochondria, Mutation.
- Humans, Nucleic Acid Conformation.
Abstract
5-Taurinomethyluridine (τm(5)U) and 5-taurinomethyl-2-thiouridine (τm(5)s(2)U) are located at the wobble position of human mitochondrial (hmt) tRNA(Leu(UUR)) and tRNA(Lys), respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys) are responsible for the loss of the discussed modifications and, as a consequence, for the occurrence of severe mitochondrial dysfunctions (MELAS, MERRF). Synthetic oligoribonucleotides bearing modified nucleosides are a versatile tool for studying mechanisms of genetic message translation and accompanying pathologies at nucleoside resolution. In this paper, we present site-specific chemical incorporation of τm(5)U and τm(5)s(2)U into 17-mers related to the sequence of the anticodon arms hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys), respectively employing phosphoramidite chemistry on CPG support. Selected protecting groups for the sulfonic acid (4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl) and the exoamine function (-C(O)CF3) are compatible with the blockage of the canonical monomeric units. The synthesis of τm(5)s(2)U-modified RNA fragment was performed under conditions eliminating the formation of side products of 2-thiocarbonyl group oxidation and/or oxidative desulphurization. The structure of the final oligomers was confirmed by mass spectroscopy and enzymatic cleavage data.
DOI: 10.1261/rna.044412.114
PubMed: 24757169
Affiliations:
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xml:lang="fr"><term>Conformation d'acide nucléique</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">5-Taurinomethyluridine (τm(5)U) and 5-taurinomethyl-2-thiouridine (τm(5)s(2)U) are located at the wobble position of human mitochondrial (hmt) tRNA(Leu(UUR)) and tRNA(Lys), respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys) are responsible for the loss of the discussed modifications and, as a consequence, for the occurrence of severe mitochondrial dysfunctions (MELAS, MERRF). Synthetic oligoribonucleotides bearing modified nucleosides are a versatile tool for studying mechanisms of genetic message translation and accompanying pathologies at nucleoside resolution. In this paper, we present site-specific chemical incorporation of τm(5)U and τm(5)s(2)U into 17-mers related to the sequence of the anticodon arms hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys), respectively employing phosphoramidite chemistry on CPG support. Selected protecting groups for the sulfonic acid (4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl) and the exoamine function (-C(O)CF3) are compatible with the blockage of the canonical monomeric units. The synthesis of τm(5)s(2)U-modified RNA fragment was performed under conditions eliminating the formation of side products of 2-thiocarbonyl group oxidation and/or oxidative desulphurization. The structure of the final oligomers was confirmed by mass spectroscopy and enzymatic cleavage data. </div></front></TEI><affiliations><list><country><li>Pologne</li></country></list><tree><country name="Pologne"><noRegion><name sortKey="Leszczynska, Grazyna" sort="Leszczynska, Grazyna" uniqKey="Leszczynska G" first="Grazyna" last="Leszczynska">Grazyna Leszczynska</name></noRegion><name sortKey="Leonczak, Piotr" sort="Leonczak, Piotr" uniqKey="Leonczak P" first="Piotr" last="Leonczak">Piotr Leonczak</name><name sortKey="Malkiewicz, Andrzej" sort="Malkiewicz, Andrzej" uniqKey="Malkiewicz A" first="Andrzej" last="Malkiewicz">Andrzej Malkiewicz</name><name sortKey="Wozniak, Karolina" sort="Wozniak, Karolina" uniqKey="Wozniak K" first="Karolina" last="Wozniak">Karolina Wozniak</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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