Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 21, Issue 15, Pages 4494-4501Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.05.046
Keywords
RNAi; siRNA; miRNA; Urea/thiourea; Aromatic compound
Funding
- Japan Society for the Promotion of Science (JSPS)
- Grants-in-Aid for Scientific Research [24390025] Funding Source: KAKEN
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We have developed chemically modified siRNAs and miRNAs bearing urea/thiourea-bridged aromatic compounds at their 3'-end for RNAi therapy. Chemically modified RNAs possessing urea/thiourea-bridged aromatic compounds instead of naturally occurring dinucleotides at the 3'-overhang region were easily prepared in good yields and were more resistant to nucleolytic hydrolysis than unmodified RNA. siRNAs containing urea or thiourea derivatives showed the desired knockdown effect. Furthermore, modified miR-143 duplexes carrying the urea/thiourea compounds in the 3'-end of each strand were able to inhibit the growth of human bladder cancer T24 cells. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
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