RNase P-Guiding Peptide Conjugates of Oligo(2'-O-methylribonucleotides) as Prospective Antibacterial Agents
A novel variant of the synthesis of 3'- and 5'-peptide conjugates of oligo(2'-O-methylribonucleotides) has been developed using thiol-maleimide chemistry. The method is based on the introduction of the maleimide group into an oligonucleotide using a novel bifunctional reagent, pentafluorophenyl ester of 3‑maleimidopropionic acid (MPPf), and the subsequent interaction of the resulting compound with an SH‑bearing peptide, which facilitates cell penetration. A series of RNase P-guiding 3'- and 5'-peptide conjugates of oligo(2'-O-methylribonucleotides) targeted to mRNA of the ftsZ and gyrA genes of Acinetobacter baumannii have been synthesized. The ability of these conjugates to guide the hydrolysis of model RNA targets by RNase P has been demonstrated. It has been shown that the introduction of the peptide molecule at the 5'-end of EGS oligo(2'-O-methylribonucleotides) practically does not reduce the efficiency of RNA hydrolysis by RNAse P.
Keywords:bacterial RNAse P EGS-oligonucleotides oligo(2'-O-methylribonucleotides) thiol-maleimide chemistry peptide conjugates
The authors would like to thank Prof. S. Altman for initiating the research in the field of EGS technologies at our Institute, Dr. D. Wesolowski for kindly provided plasmids to prepare components of RNase P holoenzyme, Dr. S.N. Khodyreva for the preparation of protein C5, and Dr. N.A. Moor for the preparation of M1 RNA.
The work was supported by the grant no. 17-04-01892 from the Russian Foundation for Basic Research. The synthesis and isolation of RNA were partially supported by Russian State funded budget project no. АААА-А17-117020210021-7.
COMPLIANCE WITH ETHICAL STANDARDS
This article does not contain any studies with the use of humans and animals as objects of research.
Conflict of Interests
The authors state that there is no conflict of interests.
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