Lipidated DAPEG Polymers as a Non-Toxic Transfection Agent—Influence of Fatty Acid Side Chain on Transfection Efficacy

This study describes the synthesis, interaction with DNA, and transfection efficacy of eight lipidated compounds based on a recently published non-lipidated parent molecule, an octamer of 2,3-l-Dap, carrying the guanidine group on its side chain. The compounds obtained were found to be non-toxic up to 5 µM and efficient DNA binders and showed greater transfection efficiency than the parent compound, with two leading molecules containing acetic and decanoic moieties. DLS experiments indicated two groups of interaction with DNA. One group modified by short-chain lipids (up to eight carbon atoms in the main chain) forms large structures due to the aggregation of multiple nucleic acids. The second group (from twelve to sixteen carbon atoms) with dominant condensation creates smaller forms and is less effective in transporting DNA into the cells.