Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation

Goldring, William; Jubeli, Emile; Downs, Rachael; Johnston, Adam J. S.; Khalique, Nada Abdul; Raju, Liji; Wafadari, Deena; Pungente, Michael D.

doi:10.1016/j.bmcl.2012.05.080

Cited by 11 publications

(4 citation statements)

References 35 publications

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“…Similar DCC-mediated coupling with a second carboxylic acid yielded the 1,2-diacylated derivatives 5a-d. In our hands, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) mediated removal of the PMB-protective group of 5a-d gave highly variable and low yields in the range of 0 to 29 % of the desired 1,2-diacylated alcohols 7a-d due to competing formation of the corresponding 1,3-diacylated alcohols 6a-d by 2,3-acylmigration, despite previous reports on successful use of this reagent [15][16][17]. Boron trichloride and dimethyl boron bromide have been used for the removal of the benzyl- [9] and the PMB [11,18] protective groups, respectively, of similar 1,2-diacylated glycerol derivatives with no or minimal 2,3-acylmigration.…”

Section: Synthesismentioning

confidence: 75%

“…The syntheses begun with the R-enantiomer of p-methoxybenzyl (PMB) protected glycerol 1, which may be easily synthesized from commercially available 1,2-isopropylidene-sn-glycerol, either by a procedure in which 1 is the product [15] or in analogy to reported procedures yielding products with other benzyl type protective groups [9,16]. Regioselective introduction of the fatty acid residues of the 1-acylated monoesters 2, 3 and 4 proceeded smoothly by N,N'-dicyclohexylcarbodiimide (DCC) mediated and 4-dimethylaminopyridine (DMAP) catalyzed condensation between diol 1 and the corresponding carboxylic acids.…”

Section: Synthesismentioning

confidence: 99%

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Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by 1H- and 13C-NMR in polar organic solvents

et al. 2014

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Isaksson, A. (2014). Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by (1)H-and (13)C-NMR in polar organic solvents. Analytical and Bioanalytical Chemistry, 406(19), 4735-4744. DOI: 10.1007/s00216-014-7826-4 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractVarious phosphatidylethanol (PEth) derivatives, the corresponding reversed positional isomers (RPI-PEths), lyso-PEth-16:0 and penta deuterium labeled PEth analogs (d5-PEths), were synthesized by enzyme independent synthetic routes. A general solvent system consisting of a mixture of acetone-d6 and methanol-d4 (97:3; v:v)

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Section: Synthesismentioning

confidence: 75%

Section: Synthesismentioning

confidence: 99%

Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by 1H- and 13C-NMR in polar organic solvents

et al. 2014

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“…[35][36][37] To find out the optimal liposomes/DNA ratio, transfection experiments were performed against HEK293 cells by using mixture lipids/ DOPE ratio of 1 : 1. As shown in Fig.…”

Section: )mentioning

confidence: 99%

Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

Niyomtham

Apiratikul

Chanchang

et al. 2014

Biological & Pharmaceutical Bulletin

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Lipid-mediated delivery of DNA into cells holds great promise both for gene therapy and basic research applications. The primary approach to improving transfection efficiency is the design and synthesis of novel cationic lipids. Alternatively, using the synergistic effect of different cationic mixtures can provide another approach to increasing transfection efficiency. This paper describes the synergistic effect of lipids with different polarheads, central core structures and hydrophobic tails. The enhancement of cellular transfection into HEK293 cells was observed by combining two lipids having aminoglycerol and di(hydroxylethyl)amino core structures at a 1 : 1 weight ratio. Additionally, the liposome formation of these lipids with the helper lipid, 1,2-dioleoyl-propyl-3-phosphatidylethanolamine (DOPE), at the weight ratio of 1 : 1 can provide higher transfection efficiency into HEK293, MCF-7 and HeLa cells than Lipofectamine™ 2000. Our finding indicated that cationic liposomes comprised of a mixture of lipids with different polarheads, central core structures and hydrophobic tails should be very promising in liposome-mediated gene delivery in vitro and in vivo.Key words cationic liposome; synergistic effect; DNA delivery; non-viral vector.Gene therapy has gained significant attention over past two decades as an alternative method to treat genetic disorders 1,2) as well as cancers.3) One fundamental of gene therapy is the delivery system that can introduce and stabilize genetic material. Since free oligonucleotides and DNA are rapidly degraded by serum nucleases, 4) many efforts are focused on developing the carriers to protect and deliver these materials into targeted cells. Two delivery systems namely viral and non-viral vectors are currently developed to solve the problems. Viral carriers have known to be one of the most effective gene delivery methods for in vivo application. [5][6][7][8] Over one thousand gene therapy clinical trials have been completed or approved; two-thirds of which performed by viral vectors. 8)However, the limitation of viral vectors concerning toxicity, immunogenicity, scale-up procedures and their relatively small capacity for therapeutic DNA has prompted the development non-viral vectors. Delivery systems based on non-viral vectors, for example cationic lipids, dendrimers or cationic polymers, have been the focus of much recent research.9) Non-viral systems have proved to be generally less toxic or immunogenic, more easily to produce and a greater stability.Cationic liposomes are one of the most extensively studied of non-viral vectors because of their lesser immunogenic nature, ease of production and handle, and ability to deliver large pieces of DNA. Cationic liposomes, like other non-viral vectors bearing positive charge, interact with the negatively charged phosphate backbone of nucleic acids to form a compact structure and facilitate cellular uptake by endocytic routes. [10][11][12][13] Since the first application of cationic lipid in DNA delivery, 14) numerous cationic lipids...

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“…On the other hand, cationic surfactants are used as corrosion inhibitors for metals in acidic environments . Recently, cationic surfactants have generated increasing interest that these types of compounds may be used as non‐viral vectors to transfer DNA into mammalian cells . This process is known as gene therapy or gene transfection.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Alkyl‐Sulfanyl 1,3,4‐Oxadiazolyl‐1,3,5,7‐Tetraazatricyclic Ammonium Chloride Type Cationic Surfactants

Yıldırım

2014

Journal of Heterocyclic Chem

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Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation

Cited by 11 publications

References 35 publications

Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by 1H- and 13C-NMR in polar organic solvents

Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by 1H- and 13C-NMR in polar organic solvents

Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

Synthesis of Novel Alkyl‐Sulfanyl 1,3,4‐Oxadiazolyl‐1,3,5,7‐Tetraazatricyclic Ammonium Chloride Type Cationic Surfactants

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