Multivalent RNA‐Cleaving Agents on a Cubic Octameric Silsesquioxane Core
- 1Department of Chemistry University of Turku Turku Finland
Abstract
Selective RNA cleavage could provide versatile options in therapeutic applications. In this study, multivalent RNA‐cleaving agents, featuring 1,5,9‐triazacyclododecane or guanidine groups as catalytic centers, were synthesized on a cubic octameric silsesquioxane (COSS) core. Their catalytic efficiencies were first evaluated and compared in the presence and absence of metal ions Zn2+, Cu2+, and Pd2+ using hexaribonucleotide models. COSS–lysine(N3)–TACD–Zn2+ 8 exhibited base moiety selectivity for uracil bases, resulting in half‐lives of 2–11 h for the cleavage of the uracil‐containing hexaribonucleotides. Then, the cleavage of a biologically relevant HER2 mRNA model sequence was studied with the most effective catalysts. Surprisingly, an organocatalyst (COSS–lysine(N3)–arginine) outperformed a metal–organic catalyst (COSS–lysine(N3)–TACD–Zn2+ 8) in catalytic efficiency, the half‐lives being 14 and 31 h, respectively. In addition, the cleavage sites of the HER2 mRNA model were determined. While the COSS–lysine(N3)–TACD–Zn2+ 8 produced high background cleavage, the organic catalysts COSS–lysine(N3)–arginine and COSS–lysine(N3)–guanidine exhibited clear site‐specificity in the HER2 mRNA cleavage. Additionally, a correlation between the reaction rates and the amount of the catalysts was verified by varying the catalyst concentrations. Fast reaction rates and site‐specificity of the cleavage indicate good potential for further development of these cleaving agents.
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BibTeX
@article{haapsaari2026multivalent,
title = {{Multivalent RNA‐Cleaving Agents on a Cubic Octameric Silsesquioxane Core}},
author = {Hanni Haapsaari and Iris Tuomi and Pasi Virta},
journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)},
year = {2026},
month = aug,
doi = {10.1002/chem.71524},
url = {https://doi.org/10.1002/chem.71524},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multivalent RNA‐Cleaving Agents on a Cubic Octameric Silsesquioxane Core
AU - Hanni Haapsaari
AU - Iris Tuomi
AU - Pasi Virta
PY - 2026
DA - 2026/08/08
JO - Chemistry (Weinheim an Der Bergstrasse, Germany)
DO - 10.1002/chem.71524
UR - https://doi.org/10.1002/chem.71524
AB - Selective RNA cleavage could provide versatile options in therapeutic applications. In this study, multivalent RNA‐cleaving agents, featuring 1,5,9‐triazacyclododecane or guanidine groups as catalytic centers, were synthesized on a cubic octameric silsesquioxane (COSS) core. Their catalytic efficiencies were first evaluated and compared in the presence and absence of metal ions Zn2+, Cu2+, and Pd2+ using hexaribonucleotide models. COSS–lysine(N3)–TACD–Zn2+ 8 exhibited base moiety selectivity for uracil bases, resulting in half‐lives of 2–11 h for the cleavage of the uracil‐containing hexaribonucleotides. Then, the cleavage of a biologically relevant HER2 mRNA model sequence was studied with the most effective catalysts. Surprisingly, an organocatalyst (COSS–lysine(N3)–arginine) outperformed a metal–organic catalyst (COSS–lysine(N3)–TACD–Zn2+ 8) in catalytic efficiency, the half‐lives being 14 and 31 h, respectively. In addition, the cleavage sites of the HER2 mRNA model were determined. While the COSS–lysine(N3)–TACD–Zn2+ 8 produced high background cleavage, the organic catalysts COSS–lysine(N3)–arginine and COSS–lysine(N3)–guanidine exhibited clear site‐specificity in the HER2 mRNA cleavage. Additionally, a correlation between the reaction rates and the amount of the catalysts was verified by varying the catalyst concentrations. Fast reaction rates and site‐specificity of the cleavage indicate good potential for further development of these cleaving agents.
SN - 0947-6539
SN - 1521-3765
ER -