Site-Specific Cleavage of RNAs Derived from the PIM1 3'-UTR by a Metal-Free Artificial Ribonuclease

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Felix ZellmannMichael W Göbel

Abstract

Oligonucleotide conjugates of tris(2-aminobenzimidazole) have been reported previously to cleave complementary RNA strands with high levels of sequence and site specificity. The RNA substrates used in these studies were oligonucleotides not longer than 29-mers. Here we show that ~150⁻400-mer model transcripts derived from the 3'-untranslated region of the PIM1 mRNA reacted with rates and specificities comparable to those of short oligonucleotide substrates. The replacement of DNA by DNA/LNA mixmers further increased the cleavage rate. Tris(2-aminobenzimidazoles) were designed to interact with phosphates and phosphate esters. A cell, however, contains large amounts of phosphorylated species that may cause competitive inhibition of RNA cleavage. It is thus important to note that no loss in reaction rates was observed in phosphate buffer. This opens the way to in-cell applications for this type of artificial nuclease. Furthermore, we disclose a new synthetic method giving access to tris(2-aminobenzimidazoles) in multigram amounts.

References

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Citations

May 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga PatutinaMarina Zenkova
May 20, 2020·Chemistry & Biodiversity·Mathias BolzMichael W Göbel
Apr 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Felix Zellmann, Michael W Göbel
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yaroslav StaroseletzMarina Zenkova
Oct 1, 2021·Chemical Communications : Chem Comm·Olivia LuigeRoger Strömberg

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Methods Mentioned

BETA
antisense oligonucleotides
PCR
in vitro transcription
electrophoresis
Cleavage
Assay

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