TY - JOUR

T1 - RNase P-Guiding Peptide Conjugates of Oligo(2'-O-methylribonucleotides) as Prospective Antibacterial Agents

AU - Danilin, N. A.

AU - Koroleva, L. S.

AU - Novopashina, D. S.

AU - Venyaminova, A. G.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - bacterial RNAse P

KW - EGS-oligonucleotides

KW - oligo(2'-O-methylribonucleotides)

KW - peptide conjugates

KW - thiol-maleimide chemistry

UR - http://www.scopus.com/inward/record.url?scp=85077867175&partnerID=8YFLogxK

U2 - 10.1134/S106816201906013X

DO - 10.1134/S106816201906013X

M3 - Article

AN - SCOPUS:85077867175

VL - 45

SP - 825

EP - 832

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 6

ER -