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Click Conjugates of Artificial Ribonucleases: Sequence Specific Cleavage with Multiple Turnover
Author(s) -
Weber Sandra,
Weinrich Timo,
Scheffer Ute,
Kalden Elisabeth,
Göbel Michael W.
Publication year - 2025
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202500451
Abstract The azido modified RNA cleaving catalyst 2 has been attached to oligonucleotides containing alkyne linkers in a central position. The resulting conjugates hybridize specifically with complementary RNA strands and cleave them with multiple substrate turnover. RNA half‐lives are in the range of 6–7 hours (pH 8, 37 °C). Some well‐placed locked nucleic acid (LNA) nucleotides can further increase substrate affinities and reaction rates significantly ( t ½ of 3.5 hours, k obs = 0.20 h −1 ). RNA cleavage does not require metal ions and runs equally well in the presence of EDTA. Fragments of precisely defined lengths are formed, well suited for subsequent analysis by mass spectrometry and related bioanalytical techniques.