Accepted_test

Novel conjugates of phosphorylguanidine oligonucleotides with bisimidazol-containing peptidomimetics
by Pavlova A. | Dyudeeva E. | Koroleva L. | Grigoryeva E. | Dmitrienko E. | Koval O. | Pyshnyi D. | Pyshnaya I | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS | Institute of Chemical Biology and Fundamental Medicine SB RAS
Abstract ID: 446
Event: BGRS-abstracts
Sections: [Sym 9] Section “Molecular Pathology, Diagnostics, and Therapeutics”

The attachment of low-molecular-weight bioreactive compounds that cleave phosphodiester bonds in RNA to antisense oligonucleotides is a relevant area in biomedicine for the development of new agents based on them and/or increasing their efficacy. Synthesis of conjugates of modified oligonucleotides with RNA-cleaving groups represents a special task, as it can expand the possibilities of their application. In this work using previously obtained phosphoramidites, a solid-phase version of azide-alkyne cycloaddition catalysed by monovalent copper ions was proposed for the synthesis of conjugates of oligodeoxyribonucleotides, including those containing phosphorylguanidine modifications, with residues of bisimidazole-containing peptidomimetics, and the method was validated for a number of nucleotide sequences. Using short RNA targets in vitro, it was shown that the introduction of phosphorylguanidine modifications to the oligonucleotide can increase the degree of RNA cleavage by these conjugates. Using cell culture, it has been shown that the attachment of bisimidazole-containing peptidomimetics to the antisense oligonucleotides does not adversely affect the efficiency of silencing EGFP expression levels.