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 (LAE L-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 a-helical 4(3)E had higher membrane-pe rturbation activity at acidic conditions compared with neutral conditi ons, When 4(3)E was incorporated with plasmid DNA-cationic peptide com plex that utilizes an endocytosis pathway for uptake into cultured cel ls, high transfection efficiency was observed, indicating that 4(3)E c an 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 p eptide effectively disrupts the endosomal membrane and increases the p opulation of the complex which could transfer to cytosol. The small ly sosome-disruptive peptide is very probably useful as the enhancer mole cule for the gene transfer techniques mediated by the endocytosis path way. (C) 1997 Academic Press.