34494-26-3Relevant academic research and scientific papers
In vivo studies of dialkynoyl analogues of DOTAP demonstrate improved gene transfer efficiency of cationic liposomes in mouse lung
Fletcher, Steven,Ahmad, Ayesha,Perouzel, Eric,Heron, Andrew,Miller, Andrew D.,Jorgensen, Michael R.
, p. 349 - 357 (2006)
A novel set of dialkynoyl analogues of the cationic, gene delivery lipid DOTAP (1) was synthesized. Structure-activity studies demonstrate that replacement of the cis-double bonds of DOTAP with triple bonds in varying positions alters both the physical properties of the resultant cationic liposome-DNA complexes and their biological functionalities, both in vitro and in vivo. Particularly, in vivo studies demonstrate that pDNA transfection of mouse lung endothelial cells with lead analogue DS(14-yne)TAP (4):cholesterol lipoplexes exhibits double the transfection level with less associated toxicity relative to the well-established DOTAP:cholesterol system. In fact, 4:cholesterol delivers up to 3 times the dose of pDNA in mice than can be tolerated by DOTAP, leading to nearly 3 times greater marker-gene expression. X-ray diffraction studies suggest that lipoplexes containing analogue 4 display increased stability at physiological temperatures. Our results thus suggest that analogue 4 is a potentially strong candidate for the gene therapy of lung tumors.
Properties of unusual phospholipids IV: Chemoenzymatic synthesis of phospholipids bearing acetylenic fatty acids
Pisch, Sandra,Bornscheuer, Uwe T.,Meyer, Hartmut H.,Schmid, Rolf D.
, p. 14627 - 14634 (1997)
14-Octadecynoic (1) and 4-octadecynoic (2) acid were synthesized in high yields (56% and 57%) and incorporated into glycerophosphatidylcholine at sn1- and sn2-position. The head group of these phosphatidylcholines was exchanged using phospholipase D (PLD) in a biphasic system. PLD from Streptomyces antibioticus, Streptomyces sp., peanut and cabbage were studied in this transphosphatidylation reaction. Under optimized conditions (40°C, organic solvent:buffer ratio 1:1.5 (v/v), pH 5.6), the conversion of phosphatidylcholine to the corresponding phospholipids with the head groups glycerol, ethanolamine and L-serine reached 99% at 40°C in 1 h. The quantitative analysis of the transphosphatidylation reactions was performed by TLC-FID.
A dialkynoyl analogue of DOPE improves gene transfer of lower-charged, cationic lipoplexes
Fletcher, Steven,Ahmad, Ayesha,Perouzel, Eric,Jorgensen, Michael R.,Miller, Andrew D.
, p. 196 - 199 (2007/10/03)
Positively-charged gene delivery agents, such as cationic liposomes, typically prepared by mixing a cationic lipid and a neutral lipid in a 1: 1 molar ratio, exhibit a fundamental flaw: on the one hand, the charge encourages cell uptake; on the other hand, the charge leads to aggregation in vivo with anionic serum components. We herein report a more phase-stable analogue of the zwitterionic and fusogenic lipid DOPE that allows for the reduction of the cationic lipid component of the liposome from 50 to 9 mol% with almost no apparent loss in transfection activity. This reduction in charge may induce important in vivo stability whilst still imparting high cell uptake and transgene expression. The Royal Society of Chemistry 2006.
