Impacts Of Head Group Configuration On Nucleic Acids Delivery Efficiency Of Lipid Functionalized Peptidomimetics

RNA interference(RNAi)is a double-stranded RNA induced gene regulation at the post-transcriptional level,degrading the specific target mRNA,thereby down-regulating the disease-related genes.It has shown great potential for the curing of various diseases caused by the abnormal gene expression.In the clinical application of RNAi,the development of highly biocompatible,high-efficiency delivery vector is critical.Previously our laboratory has synthesized the potential nucleic acid carriers,namely DoGo2,DoGo3,DoGo4?a2?2,DoGo4?a3?1 lipoplex and so on.They are synthesized by modifying the hydrophilic head of DoGo1.In this paper,three kinds of lipid functionalized Peptidomimetics were synthesized from natural amine acid,and the impact of amino acid composition,amino acid number and the type of amine on their delivery efficiency were studied.The structures and molecular weights of the compounds(DoGo6,DoGo311,DoGol21)were determined by 1H-NMR and MS.The lipoplex were characterized by transmission electron microscopy,electromotive force and laser particle size.We studied the biological activity of DoGo6,DoGo311,DoGo121 lipoplex.The experimental results show that their biocompatibility is better than the commercial transfection reagent Lipofectamine 2000.DoGo6,DoGo311 lipoplex can bind to dsDNA at a lower phosphoric acid group(P)/amino(N)ratio.In vitro transfection experiments incldued plasmids transfection as well as siRNA(siGAPDH,siPLKl)transfection.The results showed that the transfection efficiency of DNA/siRNA was increased with the increasing number of amino acids in the head group,and the DoGo6 lipid complex had highest potential for targeting various cells including 293T,HeLa and HepG2 cells.