Synthesis of Novel Cationic Lipids: Effect of Structural Modification on the Efficiency of Gene Transfer

• DOI: 10.1021/jm010918g
• Publication Date: 2002-07-26T04:45:26Z
• Authors: James A. Heyes; Dan Niculescu-Duvaz; Robert G. Cooper; Caroline J. Springer
• Keywords: Cationic polymerization; Phosphatidylethanolamine

A series of novel cationic lipids was designed and synthesized in an effort to understand the importance various structural features with respect transfection efficiency. Particular attention has been paid hydrophobic domain headgroup. An efficient method synthesizing asymmetric diether is described, using alkyl chains ranging from C12 C18 unsaturated oleyl group. The ternary formulations including lipid 3β-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol) dioleoyl phosphatidylethanolamine (DOPE) were up 10-fold more efficacious vitro assays than DC-Chol/DOPE control. shorter most performed best. chemical nature basicity headgroups have varied by coupling four naturally occurring amino acids side chainsarginine, histidine, lysine, tryptophan. Transfection efficiency highest for arginine/lysine derivatives, binary containing acid derivative alone DOPE proving superior.