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Conjugates of RNase P-Guiding Oligonucleotides with Oligo( N -Methylpyrrole) as Prospective Antibacterial Agents
Russian Journal of Bioorganic Chemistry ( IF 1.1 ) Pub Date : 2021-04-26 , DOI: 10.1134/s1068162021020084
N. A. Danilin , A. L. Matveev , N. V. Tikunova , A. G. Venyaminova , D. S. Novopashina

Abstract

The conjugates of RNase P guiding oligo(2'-O-methylribo)- and oligodeoxyribonucleotides (EGS oligonucleotides) with oligo(N-methylpyrrole) have been synthesized for the first time. The ability of RNase P to hydrolyze RNA in the presence of EGS oligonucleotides and their conjugates with oligo(N-methylpyrrole) has been demonstrated in model systems using fluorescently labeled chemically synthesized oligoribonucleotides corresponding to the fragments of mRNA of the ftsZ and gyrA genes of Acinetobacter baumannii. It has been shown that hydrolysis of RNA by RNase P occurs more efficiently in the presence of the conjugates than in the case of unmodified oligodeoxyribonucleotides. The introduction of oligo(N-methylpyrrole) in EGS oligo(2'-O-methylribonucleotides) insignificantly changes the effectiveness of hydrolysis. It has been demonstrated that the cell-penetrating ability of oligonucleotides is enhanced because of the presence of oligo(N-methylpyrrole) at the 5'-end.



中文翻译:

RNase P指导寡核苷酸与寡聚(N-甲基吡咯)作为预期的抗菌剂的缀合物

摘要

首次合成了RNase P引导寡(2'- O-甲基核糖)-和寡脱氧核糖核苷酸(EGS寡核苷酸)与寡核苷酸(N-甲基吡咯)的结合物。在模型系统中使用荧光标记的化学合成的寡核糖核苷酸(对应于不动杆菌ftsZgyrA基因的mRNA片段)在模型系统中证明了RNase P在EGS寡核苷酸及其与寡核苷酸(N-甲基吡咯)结合物存在下水解RNA的能力。鲍曼尼已经显示,在缀合物存在下,与未修饰的寡脱氧核糖核苷酸相比,RNA酶P更有效地发生RNA水解。在EGS寡聚(2'- O-甲基核糖核苷酸)中引入寡聚(N-甲基吡咯)不会显着改变水解的有效性。已经证实,由于在5'-末端存在寡聚(N-甲基吡咯),寡核苷酸的细胞穿透能力得以增强。

更新日期:2021-04-27
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