1987 Fiscal Year Final Research Report Summary
Chemical Synthesis of RNAs Containing Lariat Structure
| Project/Area Number |
61470031
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
天然物有機化学
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
HATA Tsujiaki The Graduate School at Natatsuta. T.I.T. Professor, 大学院総合理工学研究所, 教授 (00016049)
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| Co-Investigator(Kenkyū-buntansha) |
SEKINE Mitsuo The Graduate School at Nagatsuta. T.I.T. Associate, 大学院総合理工学研究所, 助手 (40111679)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Lariat Structure / Branched RNA / Phosphotriester Approach / Phosphorylation / RNAの化学合成 |
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| Research Abstract |
In the aim to synthesize the lariat structure of RNA found in Splicing products In eukaryotic cells, chemical synthesis of a hexaribonucleotide CUGA^A_ involving the branched point of adenosine, was achieved throughout this study. For regioselective introduction of two different phosphoryl groups at the 2', and 3' positions, the first phosphorylation was done by the reaction of N^6-benzoly1-3',5'-O-(tetraisopropyldi- siloxane-1,3-diyl) adenosine with tris(diethylamino)phosphine in the presence of tetrazole followed by addition of aniline and subsequent oxidation with iodine. Fluoride ion-catalyzed desilylation of the resulting product gave a mixture of 2'- and 3'-(dianilino)phosphorylated species, from which the 3'-regioisomer was crystalized and used for the second phosphorylation after the 5'-tritylation. The bis(cyanoethoxy) phosphoryl group was chosen as the secong phosphoryl residue. The diphosphorylated unit thus obtained was used for chain elongation in the 2' and 3' direction by using selective removal of the phenylthio group or the cyanoethyl group. The subsequent detritylation followed by condensation with a timer block which had a phosphodiester residue at the 3'-terminus gave a fully protected CUGA^A_ sequence in good yield. Deprotection of all the protecting groups afforded the desired unprotgected branched hexamer of CUGA^A_ in 32% yield. The inhibitory effect of this synthetic branched RNA on splicing reaction was tested. Consequently, almost no inhibition was observed.
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[Publications] H,Tanimura, T,Fukazawa, M,Sekine, T,Hata, J,W,Efcavitch, and G,Zon: "The Practical Synthesis of RNA Fragments in the Solid Phase Approach." Tetrahedron Lett.29. 577-578 (1988)
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