Conjugates of RNase P-Guiding Oligonucleotides with Oligo(N-Methylpyrrole) as Prospective Antibacterial Agents

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.