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


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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.

Sobre autores

N. Danilin

Novosibirsk State University

Email: danov@niboch.nsc.ru
Rússia, Novosibirsk, 630090

L. Koroleva

Novosibirsk State University; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: danov@niboch.nsc.ru
Rússia, Novosibirsk, 630090; Novosibirsk, 630090

D. Novopashina

Novosibirsk State University; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Autor responsável pela correspondência
Email: danov@niboch.nsc.ru
Rússia, Novosibirsk, 630090; Novosibirsk, 630090

A. Venyaminova

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: danov@niboch.nsc.ru
Rússia, Novosibirsk, 630090

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