Document Detail


Synthesis and silencing properties of siRNAs possessing lipophilic groups at their 3'-termini.
MedLine Citation:
PMID:  18644731     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Short-interfering RNAs (siRNAs) conjugated with lipophilic groups at their 3'-termini were synthesized. The properties of the synthesized siRNAs were examined in detail, and it was found that at low concentrations, their silencing abilities were dependent on the positions of the modifications and the types of organic molecules attached. Although the modification of siRNAs with palmitic acid or oleic acid at the 3'-end slightly reduced their silencing activities, siRNAs had enough abilities to induce RNAi at 10 nM concentrations. On the other hand, the modification of siRNAs with cholesterol at the 3'-end of the passenger strand was tolerated; however, the modification at the guide strand significantly reduces its silencing activity. The siRNAs modified with the lipophilic groups did not possess ability to penetrate the plasma membranes of HT-1080 cells without the transfection reagent. However, the results described in this report will aid in designing novel siRNAs with cell membrane-permeable molecules.
Authors:
Yoshihito Ueno; Koshi Kawada; Tomoharu Naito; Aya Shibata; Kayo Yoshikawa; Hye-Sook Kim; Yusuke Wataya; Yukio Kitade
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  16     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-18     Completed Date:  2008-10-29     Revised Date:  2011-06-17    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  7698-704     Citation Subset:  IM    
Affiliation:
Department of Biomolecular Science, Faculty of Engineering, Gifu University, Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. uenoy@gifu-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cholesterol / chemistry,  pharmacology
Endoribonucleases / metabolism
Hela Cells
Humans
Lipids / chemical synthesis,  chemistry*,  pharmacology
Magnetic Resonance Spectroscopy
Oleic Acids / chemistry,  pharmacology
Palmitic Acids / chemistry,  pharmacology
RNA Interference
RNA, Small Interfering / chemical synthesis*,  chemistry*,  genetics,  pharmacology
Transfection
Chemical
Reg. No./Substance:
0/Lipids; 0/Oleic Acids; 0/Palmitic Acids; 0/RNA, Small Interfering; 57-88-5/Cholesterol; EC 3.1.-/Endoribonucleases; EC 3.1.26.-/2-5A-dependent ribonuclease

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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