Linked Life Data

9572871

Source:http://linkedlifedata.com/resource/pubmed/id/9572871

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1998-6-8
pubmed:abstractText
The preparation of cationic amphiphiles that induce minor cytotoxic response during polynucleotide delivery into mammalian cells has been limited by the conventional use of ester, amide, or carbamate linkages to tether either the polar or the hydrophobic domains. The deleterious effects of ammonium-based lipidic salts on cellular processes have been well-established. The present report is the first example of a linchpin tetraester construct that utilizes ester linkages to tether both the polar and hydrophobic domains. Dimyristoyl and dioleoyl analogues were prepared from pentaerythritol, N,N-dimethylglycine, and their corresponding fatty acyl groups via successive diesterifications followed by amine quaternization. The resultant cationic tetraesters were examined in transfection (luciferase) and cell proliferation (MTS) assays using NIH 3T3 and 16HBE14o- cells. The tetraesters exhibited transfection activity comparable to the well-studied lipids DOTAP and DC-cholesterol (DC-chol) in both cell lines. The tetraester construct afforded no cytotoxicity in NIH3T3 cells and provided a significant lowering of cytotoxicity relative to DC-chol in the 16HBE14o- cells. The expression of green fluorescent protein (GFP) in both cell lines also was examined using the lipid panel. Comparison of fluorescent and corresponding phase-contrast images confirmed the chemical cytotoxicity results and revealed that the cytotoxic response was not dependent on transgene expression. Phase-contrast micrographs of cells treated with the cationic lipid panel in the absence of GFP plasmid showed identical morphology to the GFP-transfected cells, suggesting that the onset of a lipid-mediated cytotoxic response might occur at a stage prior to endosomal encapsulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,2-dioleoyloxy-3-(trimethylammonium..., http://linkedlifedata.com/resource/pubmed/chemical/3-(N-(N',N'-dimethylaminoethane)carb..., http://linkedlifedata.com/resource/pubmed/chemical/Cations, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Monounsaturated, http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Lipids, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Surface-Active Agents
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6533-40
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
A novel tetraester construct that reduces cationic lipid-associated cytotoxicity. Implications for the onset of cytotoxicity.
pubmed:affiliation
Department of Chemistry, University of California, Davis, California 95616, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't