Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNALeu(UUR) and tRNALys

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dc.contributor.authorLeszczyńska, Grażyna
dc.contributor.authorLeonczak, Piotr
dc.contributor.authorWoźniak, Karolina
dc.contributor.authorMałkiewicz, Andrzej
dc.date.accessioned2016-02-01T12:51:23Z
dc.date.available2016-02-01T12:51:23Z
dc.date.issued2014
dc.description.abstract5-Taurinomethyluridine (τm5U) and 5-taurinomethyl-2-thiouridine (τm5s2U) are located at the wobble position of human mitochondrial (hmt) tRNALeu(UUR) and tRNALys, respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNALeu(UUR) and hmt-tRNALys 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 τm5U and τm5s2U into 17-mers related to the sequence of the anticodon arms hmt-tRNALeu(UUR) and hmttRNALys, 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 τm5s2U-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.en_EN
dc.identifier.citationRNA, Vol. 20, nr 6, s. 938-947
dc.identifier.issn1355-8382
dc.identifier.otherISSN (online) 1469-9001
dc.identifier.urihttp://hdl.handle.net/11652/1031
dc.identifier.urihttp://rnajournal.cshlp.org/content/20/6/938.full
dc.language.isoenen_EN
dc.publisherCold Spring Harbor Laboratory Pressen_EN
dc.relation.ispartofseriesRNA, Vol. 20, nr 6en_EN
dc.subjecthuman mitochondrial tRNAen_EN
dc.subjectmodified ribonucleosidesen_EN
dc.subject5-taurinomethyluridineen_EN
dc.subject5-taurinomethyl-2-thiouridineen_EN
dc.subjectphosphoramidite chemistryen_EN
dc.titleChemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNALeu(UUR) and tRNALysen_EN
dc.typeArtykułpl_PL
dc.typeArticleen_EN

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