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靶向小鼠逆转录病毒多聚嘌呤序列的三链螺旋

Triple-helices targeted to the polypurine tract of a murine retrovirus.

作者信息

Porumb H, Dagneaux C, Letellier R, Malvy C, Taillandier E

机构信息

Laboratoire de Spectroscopie Bio-moléculaire C.S.S.B., URA CNRS 1430, Université Paris Nord, Bobigny, France.

出版信息

Gene. 1994 Nov 4;149(1):101-7. doi: 10.1016/0378-1119(94)90417-0.

Abstract

The all-purine 13-mer oligodeoxyribonucleotide d(GGGGGGAAAAAGA), containing an unusually large block of contiguous guanines, was shown by electrophoresis and thermoelution to form a specific, 'antiparallel' complex with the duplex containing the polypurine tract of murine retroviruses. Fourier transform infra-red spectroscopy (FTIR) and molecular modeling indicated that the complex is based on reverse Hoogsteen G(GC) and A(AT) triplets, with anti orientations of the bases and with all the strands having S-type sugar conformations. This G + A-containing 13-mer and a G + T-containing 22-mer, d(TGTTTGTTTGGGGGGTTTTTGT), aimed at the same target, retarded in a sequence-specific manner the spreading of the Friend retrovirus in Dunni cells infected de novo, thus indicating that the polypurine tract of retroviruses may be a suitable target for anti-gene action.

摘要

全嘌呤13聚体寡脱氧核糖核苷酸d(GGGGGGAAAAAGA)含有异常大的连续鸟嘌呤片段,通过电泳和热洗脱显示其与包含鼠逆转录病毒多嘌呤序列的双链体形成特定的“反平行”复合物。傅里叶变换红外光谱(FTIR)和分子模拟表明,该复合物基于反向Hoogsteen G(GC)和A(AT)三联体,碱基呈反式构象,所有链均具有S型糖构象。这个含G+A的13聚体和一个含G+T的22聚体d(TGTTTGTTTGGGGGGTTTTTGT)靶向同一靶点,以序列特异性方式抑制Friend逆转录病毒在新生感染的邓尼细胞中的传播,从而表明逆转录病毒的多嘌呤序列可能是反基因作用的合适靶点。

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