Document Detail


Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery.
MedLine Citation:
PMID:  19932970     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Twenty-four asymmetric divalent head group cholesterol-based cationic lipids were designed and synthesized by parallel solid phase chemistry. These asymmetric head groups composed of amino functionality together with trimethylamino, di(2-hydroxyethyl)amino or guanidinyl groups. Spacers between cationic heads and linker were both equal and unequal in length. These lipids were subjected to evaluation for DNA binding affinities by gel retardation assay and were screened for their transfection efficiency on HEK293 cells. Cationic lipids with equal chain length exhibited high transfection efficiency when polar part contained asymmetric polar heads. In contrast, lipids with unequal chain length exhibited high transfection efficiency when polar part contained symmetric heads. According to the optimal formulation, seven lipids exhibited higher transfection efficiency than the commercially available transfection agents, Effectene, DOTAP and DC-Chol, to deliver DNA into PC3 human prostate adenocarcinoma cells. 3beta-[N-(N'-Guanidinyl)-2'-aminoethyl)-N-(2-aminoethyl)carbamoyl] cholesterol (5) bearing amino and guanidinyl polar heads exhibited highest transfection efficiency with minimal toxicity. The morphology of active liposomes was observed by transmission electron microscopy (TEM) and size of liposomes were around 200-700 nm.
Authors:
Widchaya Radchatawedchakoon; Ramida Watanapokasin; Aungkana Krajarng; Boon-ek Yingyongnarongkul
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-31
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-04-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  330-42     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkapi, Bangkok 10240, Thailand.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Cations / chemical synthesis,  chemistry*
Cell Line
Cell Line, Tumor
Cholesterol / chemical synthesis,  chemistry*
DNA / administration & dosage*,  chemistry
Humans
Lipids / chemical synthesis,  chemistry*
Liposomes / chemistry
Phosphatidylethanolamines / chemical synthesis,  chemistry
Serum / chemistry
Transfection*
Chemical
Reg. No./Substance:
0/1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; 0/Cations; 0/Lipids; 0/Liposomes; 0/Phosphatidylethanolamines; 57-88-5/Cholesterol; 9007-49-2/DNA

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


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