Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

Friederike Danneberg,Michael W Göbel,Roger Strömberg,Elisabeth Kalden,Alice Ghidini,Plamena Dogandzhiyski

doi:10.3762/bjoc.11.55

Friederike Danneberg, Michael W Göbel + Show 4 more

Open Access

https://doi.org/10.3762/bjoc.11.55

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Abstract

Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are effective site-specific RNA cleavers. Their mechanism of action is independent of metal ions. Here we investigate conjugates with peptide nucleic acids (PNA). RNA degradation occurs with similar rates and substrate specificities as in experiments with DNA conjugates we performed earlier. Although aggregation phenomena are observed in some cases, proper substrate recognition is not compromised. While our previous synthesis of 2-aminobenzimidazoles required an HgO induced cyclization step, a mercury free variant is described herein.

Highlights

Sequence specific artificial ribonucleases are an attractive research target for several reasons
Most site-selective artificial ribonucleases consist of a catalytic unit attached to a DNA oligonucleotide or 2’-O-methyloligoribonucleotide complementary to the targeted RNA [1,2,3], possible future in cell applications suggest the conjugation of RNA cleavers to oligonucleotide analogues such as peptide nucleic acids (PNA) [4]
We have shown that PNA conjugates of tris(2-aminobenzimidazole) are potent hydrolytic cleavers of RNA, exhibiting similar efficiency and substrate specificity as the corresponding DNA conjugates tested previously

Summary

Introduction

Sequence specific artificial ribonucleases are an attractive research target for several reasons. PNA conjugates of both metal-containing and metal-free RNA cleavers have been effectively used as artificial nucleases towards different substrates [8,9,10,11]. We decided to investigate the activity of tris(2-aminobenzimidazole) [15] – a metal-free ribonuclease developed by us formerly – as a conjugate with PNA.

Results

Conclusion