The enhancing effect of anionic alpha-helical peptide on cationic peptide-mediating transfection systems

A peptide consisting of 12 amino acids including 3 glutamic acids (LAEL-LAEL-LAEL; 4(3)E) underwent pH-dependent conformational change from random coil to alpha-helix when the pH was decreased from 7.4 to 5.0 in the presence of egg PC. This alpha-helical 4(3)E had higher membrane-perturbation activity at acidic conditions compared with neutral conditions. When 4(3)E was incorporated with plasmid DNA-cationic peptide complex that utilizes an endocytosis pathway for uptake into cultured cells, high transfection efficiency was observed, indicating that 4(3)E can enhance the transfection activity of cationic peptide. It is likely that 4(3)E in the multi-complex of the plasmid DNA and the cationic peptide effectively disrupts the endosomal membrane and increases the population of the complex which could transfer to cytosol. The small lysosome-disruptive peptide is very probably useful as the enhancer molecule for the gene transfer techniques mediated by the endocytosis pathway.