Document Detail


Efficient nucleic acid transduction with lipoplexes containing novel piperazine- and polyamine-conjugated cholesterol derivatives.
MedLine Citation:
PMID:  19028097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To advance the use of cationic lipids for non-viral nucleic acid vector formulation, a panel of novel nitrogen heterocycle cholesteryl derivatives containing a biodegradable carbamate linker was synthesised. Optimally acting piperazine and cyclen compounds had nucleic acid-binding and lipoplex nanoparticle formation properties that were suitable for their use as non-viral vectors. It was found that the lipoplexes formed were capable of efficient non-toxic nucleic acid delivery to cells in culture. The chemical structure of individual cationic lipids, which is likely to influence lipoplex formation, affected efficiency of DNA or RNA transfection. The results indicated that the cyclen containing compound possessing two cholesteryl moieties resulted in efficient siRNA-mediated target gene silencing but was a poor reagent for DNA transfection.
Authors:
Rafique Ul Islam; Justin Hean; Willem A L van Otterlo; Charles B de Koning; Patrick Arbuthnot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-06
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  19     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-26     Completed Date:  2009-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  100-3     Citation Subset:  IM    
Affiliation:
Department of Molecular Medicine and Haematology, Antiviral Gene Therapy Research Unit, University of the Witwatersrand Medical School, Private Bag 3, WITS, South Africa.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cations
Cells / metabolism
Cholesterol Esters / chemistry*
DNA / pharmacokinetics
Heterocyclic Compounds / chemistry*
Humans
Lipids / chemistry
Piperazines / chemistry*
Polyamines / chemistry*
RNA / pharmacokinetics
RNA, Small Interfering / pharmacokinetics
Transduction, Genetic / methods*
Chemical
Reg. No./Substance:
0/Cations; 0/Cholesterol Esters; 0/Heterocyclic Compounds; 0/Lipids; 0/Piperazines; 0/Polyamines; 0/RNA, Small Interfering; 294-90-6/cyclen; 63231-63-0/RNA; 9007-49-2/DNA

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


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