RNase P-Guiding Peptide Conjugates of Oligo(2'-O-methylribonucleotides) as Prospective Antibacterial Agents

N. A. Danilin, L. S. Koroleva, D. S. Novopashina, A. G. Venyaminova

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)825-832
Number of pages8
JournalRussian Journal of Bioorganic Chemistry
Volume45
Issue number6
DOIs
Publication statusPublished - 1 Nov 2019

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Keywords

  • bacterial RNAse P
  • EGS-oligonucleotides
  • oligo(2'-O-methylribonucleotides)
  • peptide conjugates
  • thiol-maleimide chemistry

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