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简并核糖核苷酸类似物rPTP的合成及RNA聚合酶掺入

Synthesis and RNA polymerase incorporation of the degenerate ribonucleotide analogue rPTP.

作者信息

Moriyama K, Negishi K, Briggs M S, Smith C L, Hill F, Churcher M J, Brown D M, Loakes D

机构信息

Gene Research Centre, Okayama University, Tsushima, Okayama 700, Japan, Nycomed Amersham plc, Amersham Laboratories, White Lion Road, Amersham, Buckinghamshire HP7 9LL, UK.

出版信息

Nucleic Acids Res. 1998 May 1;26(9):2105-11. doi: 10.1093/nar/26.9.2105.

Abstract

The synthesis and enzymatic incorporation into RNA of the hydrogen bond degenerate nucleoside analogue 6-(beta-d-ribofuranosyl)-3, 4-dihydro-8H-pyrimido[4,5-c]-[1,2]oxazin-7-one (P) is described. The 5'-triphosphate of this analogue is readily incorporated by T3, T7 and SP6 RNA polymerases into RNA transcripts, being best incorporated in place of UTP, but also in place of CTP. When all the uridine residues in an HIV-1 TAR RNA transcript are replaced by P the transcript has similar characteristics to the wild-type TAR RNA, as demonstrated by similar melting temperatures and CD spectra. The P-substituted TAR transcript binds to the Tat peptide ADP-1 with only 4-fold lowered efficiency compared with wild-type TAR.

摘要

描述了氢键简并核苷类似物6-(β-D-呋喃核糖基)-3,4-二氢-8H-嘧啶并[4,5-c]-[1,2]恶嗪-7-酮(P)的合成及其酶促掺入RNA的过程。该类似物的5'-三磷酸很容易被T3、T7和SP6 RNA聚合酶掺入RNA转录本中,最适合替代UTP掺入,但也可替代CTP掺入。当HIV-1 TAR RNA转录本中的所有尿苷残基都被P取代时,转录本具有与野生型TAR RNA相似的特征,如相似的解链温度和圆二色光谱所示。与野生型TAR相比,P取代的TAR转录本与Tat肽ADP-1结合的效率仅降低了4倍。

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Structural rearrangements on HIV-1 Tat (32-72) TAR complex formation.
FEBS Lett. 1996 Apr 22;384(3):255-9. doi: 10.1016/0014-5793(96)00314-6.
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Control of RNA initiation and elongation at the HIV-1 promoter.HIV-1启动子处RNA起始和延伸的调控
Annu Rev Biochem. 1994;63:717-43. doi: 10.1146/annurev.bi.63.070194.003441.

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