Synthesis, Activity, and Structure−Activity Relationship Studies of Novel Cationic Lipids for DNA Transfer

摘要: We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These were introduced into lipids. To optimize the transfection efficiency in novel series, we carried out structure-activity relationship studies by introduction variable-length lipids, linkers between lipid moiety, substituted linkers. introduce concept using within molecules as carriers side groups harboring various functionalities (side chain entity), assessed a library composed entities, additional chains, targeting groups, finally molecular probes rhodamine biotin cellular traffic studies. The activity products was assayed vitro Hela carcinoma, NIH3T3, CV1 fibroblasts vivo Lewis Lung carcinoma model. Products from series displayed high activities. Results indicated that moiety is permitted. primary physicochemical characterization DNA/lipid complexes demonstrated with this leading compound. Selected are currently being developed preclinical studies, labeled lipopolyamines can be used study intracellular DNA/cationic complexes.