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Updated: Aug 18, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Synthesis and characterization of small interfering RNAs with haloalkyl groups at their 3'-dangling ends
Akash Chandela1, Taeko Watanabe2, Kenji Yamagishi2
1The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Abstract:
With the aim to create a small interfering RNA (siRNA) with enhanced activity and resistance to nuclease degradation, we synthesized and evaluated the properties of the following siRNAs containing haloalkyl β-d-ribofuranosides at their 3'-dangling ends: 2,2,2-trifluoroethyl β-d-ribofuranoside, 2,2,2-trichloroethyl β-d-ribofuranoside and 2,2,2-tribromoethyl β-d-ribofuranoside. The gene silencing activities of the modified siRNAs were investigated through a dual luciferase reporter assay using HeLa cells. The highest silencing activity was observed for the trichloroethyl analog modified siRNA, which was closely followed by the trifluoroethyl and tribromoethyl analogs. The modified siRNAs were found to show increased binding affinity towards the Piwi-Argonaute-Zwille (PAZ) domain protein based on computational analysis and an experimental study. Furthermore, the RNAs modified with the analogs at their 3'-ends exhibited improved resistance to hydrolysis by a 3'-exonuclease.
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