Azhayeva E, Azhayev A, Auriola S, Tengvall U, Urtti A
Department of Pharmaceutical Chemistry, University of Kuopio, FIN-70211 Kuopio, Finland.
Nucleic Acids Res. 1997 Dec 15;25(24):4954-61. doi: 10.1093/nar/25.24.4954.
Several circular oligonucleotides were synthesized and characterized by electrospray ionization mass spectrometry. Experiments on termination of primer extension catalysed by DNA polymerases, Klenow fragment and Tth have demonstrated that a double helix forming circular 2'-deoxyribooligomer containing a 25mer sequence complementary to the target single-stranded DNA along with a 34mer random mismatching stretch appears to be a potent inhibitor of replication in vitro. Studies on inhibition of luciferase gene expression in a cell-free transcription-translation system have shown that a duplex forming circular 2'-deoxyribooligonucleotide containing a 25mer sequence complementary to the target mRNA and a 14mer random mismatching stretch can serve as an effective antisense compound as a standard linear complementary oligomer. Features of double helix forming circular oligonucleotides composed of 2'-deoxyribonucleosides seem to be useful for the design of new antigene and antisense agents.
合成了几种环状寡核苷酸,并通过电喷雾电离质谱对其进行了表征。关于由DNA聚合酶、Klenow片段和Tth催化的引物延伸终止实验表明,一种形成双螺旋的环状2'-脱氧核糖寡聚物,其包含与目标单链DNA互补的25聚体序列以及34聚体随机错配片段,似乎是一种有效的体外复制抑制剂。在无细胞转录-翻译系统中对荧光素酶基因表达抑制的研究表明,一种形成双链的环状2'-脱氧核糖寡核苷酸,其包含与目标mRNA互补的25聚体序列以及14聚体随机错配片段,可作为一种有效的反义化合物,如同标准的线性互补寡聚物一样。由2'-脱氧核糖核苷组成的形成双螺旋的环状寡核苷酸的特性似乎有助于新型反基因和反义药物的设计。