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 language | English |
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Pages (from-to) | 825-832 |
Number of pages | 8 |
Journal | Russian Journal of Bioorganic Chemistry |
Volume | 45 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Nov 2019 |
Keywords
- bacterial RNAse P
- EGS-oligonucleotides
- oligo(2'-O-methylribonucleotides)
- peptide conjugates
- thiol-maleimide chemistry