title: Synthesis and DNA transfection properties of new head group modified malonic acid diamides.
abstract: Malonic acid diamides with two long hydrophobic alkyl chains and a basic polar head group as a new class of non-viral gene transferring compounds have shown high transfection efficiency and moderate toxicity. Based on the results obtained with saturated and unsaturated alkyl residues new derivatives with a more complex head group structure have been synthesized. For this purpose, cationic respectively basic groups were introduced by one or two lysine residues bound via tris(aminoethyl)amine spacer to the malonic acid diamide backbone. By studying in vitro gene delivery an increase of transfection efficacy was observed when using lipids with at least one unsaturated alkyl chain. This leads to cationic lipids exhibiting comparable or even higher transfection efficacies compared to the commercially available transfection agents LipofectAmine™ and SuperFect™. Phase transitions and phase structures of selected compounds have been analyzed and discussed in terms of transfection abilities. Particle size and zeta potential of liposomes and lipoplexes were also determined.
authors.affiliation: Institute of Pharmacy, Department of Biochemical Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wölk
authors.forename: Martin
authors.initials: M
authors.lastname: Heinze
authors.forename: Patrick
authors.initials: P
authors.lastname: Kreideweiss
authors.forename: Matthias
authors.initials: M
authors.lastname: Dittrich
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.forename: Andreas
authors.initials: A
authors.lastname: Langner
authors.forename: Bodo
authors.initials: B
authors.lastname: Dobner
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D018374:LLC-PK1 Cells; D008081:Liposomes; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D044367:Phase Transition; D013552:Swine; D014162:Transfection / Q000379:methods*
chemical_list: D000577:Amides; D008081:Liposomes; D008314:Malonates; C030290:malonic acid