New amphiphilic amino acid derivatives for efficient DNA transfection in vitro

Abstract

Nucleic acids-based therapies have recently developed as next-generationagents for treating and preventing viral infection, cancer, and genetic disorders,but their use is still limited due to its relatively poor delivery into targetedcells. We designed and synthesized new amphiphilic amino acid derivatives(cysteine-based) of low molecular weight, formed by the same pentapeptide(AG2: WWCOO) N-acylated, with different hydrophobic chains containingfrom 12 to 18 carbons, named AG2-Cn (N), which dimerize by oxidationin the presence of pLenti-CMV-GFP Puro plasmid (P) in the respectivegemini. We determined transfection efficiency, critical micelle concentration,particle size, ζ-potential and cytotoxicity for the derivatives obtained. Wefound that all the synthesized compounds were active for DNA delivery andhad greater ability to transfect CHO-K1 cells. In particular, AG2-C18 is apromising carrier for gene delivery because it showed no cytotoxicity and itsactivity was greater than or equal to the commercial actives currently used.