2'-O-补骨脂素共轭寡核苷酸与具有点突变的RNA的选择性光交联
Selective photo-cross-linking of 2'-O-psoralen-conjugated oligonucleotide with RNAs having point mutations.
作者信息
Higuchi Maiko, Yamayoshi Asako, Yamaguchi Takasei, Iwase Reiko, Yamaoka Tetsuji, Kobori Akio, Murakami Akira
机构信息
Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Kyoto, Japan.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2007;26(3):277-90. doi: 10.1080/15257770701257434.
It has been reported that point mutations in genes are responsible for various cancers and the selective regulation of the gene expression is an important issue to develop a new type of anticancer drugs. In this report, we present a new type of antisense molecule that photo-cross-links to an oligoribonucleotide having a point mutation site in a sequence specific manner. 2'-O-psoralen-conjugated adenosine was synthesized in four steps from adenosine and introduced in the middle of an oligodeoxyribonucleotide (2'-Ps-oligo). Compared with 5'-O-psoralen-conjugated oligodeoxyribonucleotide (5'-Ps-oligo), which has a psoralen at the 5'-end, 2'-Ps-oligo more selectively photo-cross-linked to a pyrimidine base of the site of alteration from purine to pyrimidine in the oligoribonucleotide.
据报道，基因中的点突变与各种癌症有关，而基因表达的选择性调控是开发新型抗癌药物的一个重要问题。在本报告中，我们展示了一种新型反义分子，它能以序列特异性方式与具有点突变位点的寡核糖核苷酸发生光交联。2'-O-补骨脂素共轭腺苷由腺苷经四步合成，并引入到寡脱氧核糖核苷酸（2'-Ps-寡核苷酸）中间。与5'-末端带有补骨脂素的5'-O-补骨脂素共轭寡脱氧核糖核苷酸（5'-Ps-寡核苷酸）相比，2'-Ps-寡核苷酸更能选择性地与寡核糖核苷酸中从嘌呤变为嘧啶的改变位点的嘧啶碱基发生光交联。
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