1',2'-氧杂环丁烷约束型腺苷和鸟苷修饰寡核苷酸的合成、物理化学及生物化学研究，以及它们与相应胞苷和胸苷类似物的比较。

Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogues.

作者信息

Pradeepkumar Pushpangadan I, Cheruku Pradeep, Plashkevych Oleksandr, Acharya Parag, Gohil Suresh, Chattopadhyaya Jyoti

机构信息

Contribution from the Department of Bioorganic Chemistry, Box 581, Biomedical Center, University of Uppsala, S-75123 Uppsala, Sweden.

出版信息

J Am Chem Soc. 2004 Sep 22;126(37):11484-99. doi: 10.1021/ja048417i.

DOI:10.1021/ja048417i

PMID:15366894

Abstract

We have earlier reported the synthesis and antisense properties of the conformationally constrained oxetane-C and -T containing oligonucleotides, which have shown effective down-regulation of the proto-oncogene c-myb mRNA in the K562 human leukemia cells. Here we report on the straightforward syntheses of the oxetane-A and oxetane-G nucleosides as well as their incorporations into antisense oligonucleotides (AONs), and compare their structural and antisense properties with those of the T and C modified AONs (including the thermostability and RNase H recruitment capability of the AON/RNA hybrid duplex by Michaelis-Menten kinetic analyses, their resistance in the human serum, as well as in the presence of exo and endonucleases).

摘要

我们之前报道了含构象受限氧杂环丁烷-C和-T的寡核苷酸的合成及其反义特性，这些寡核苷酸已显示出在K562人白血病细胞中原癌基因c-myb mRNA的有效下调。在此，我们报道氧杂环丁烷-A和氧杂环丁烷-G核苷的直接合成及其掺入反义寡核苷酸（AON）中，并将它们的结构和反义特性与T和C修饰的AON（包括通过米氏动力学分析的AON/RNA杂交双链体的热稳定性和RNase H募集能力、它们在人血清中的抗性以及在外切核酸酶和内切核酸酶存在下的抗性）进行比较。