Insertion of hydrophobic spacers on dodecalysines as potential transfection enhancers

The use of cationic polymers in gene therapy aims at improving the circulation, protection and delivery nucleic acids. modification poly(L-lysine) (PLL), including insertion hydrophobic moieties, is an efficient strategy to enhance transfection efficiency this synthetic system. PLL usually modified through either extremities polymer chains or amino groups present on side chains. Herein synthesis dodecalysines as model with hexyl spacing units regularly distributed along oligomer backbone reported. Oligolysines terminated azidohexyl were prepared by solid-phase ligated copper-assisted alkyne-azide cycloaddition using propargylamine. iterative ligation α-azidohexyloligolysines was more when performed resin compared solution. plasmid DNA hydrophobically then that unmodified dodecalysine. results show formulated helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) hydrophobized exhibited a higher than one. Interestingly, could also be increased addition fusogenic peptide, which paves way for modifications oligolysines lead improved activities.