TY  - JOUR
A1  - Zellmann, Felix
A1  - Thomas, Laura
A1  - Scheffer, Ute
A1  - Hartmann, Roland K.
A1  - Göbel, Michael
T1  - Site-specific cleavage of RNAs derived from the PIM1 3′-UTR by a metal-free artificial ribonuclease
T2  - Molecules
N2  - 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.
KW  - 2-aminobenzimidazole
KW  - cleavage of large RNA molecules
KW  - cleavage site selection
KW  - DNA/LNA mixmers
KW  - dye labeling
KW  - guanidine analogs
KW  - oligonucleotides
KW  - specificity of cleavage
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50022
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-500223
SN  - 1420-3049
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
VL  - 24
IS  - 4, Art. 807
SP  - 1
EP  - 11
PB  - MDPI
CY  - Basel
ER  -