N. Ohmori et al., IMPORTANCE OF HYDROPHOBIC REGION IN AMPHIPHILIC STRUCTURES OF ALPHA-HELICAL PEPTIDES FOR THEIR GENE TRANSFER-ABILITY INTO CELLS, Biochemical and biophysical research communications, 245(1), 1998, pp. 259-265
It has been showned that cationic alpha-helical peptides can be useful
as nucleic acid-carrier molecules for gene transfer into cells. In or
der to investigate the significancemake sure of importance of the hydr
ophobic region in amphiphilic peptides in relation to their transfecti
on ability, we have employed five kinds of peptides with a systematica
lly varied hydrophobic-hydrophilic balance in the amphiphilic structur
es, and have evaluated the relationship between the structure and the
gene transfer ability of the peptides into COS-7 cells. The peptides w
ith a large hydrophobic region took alpha-helical structures, formed l
arge aggregates and showed high transfection efficiency. Their high ef
ficiency can be explained on the basis of their ability to form stable
aggregates which can be internalized by endocytosis and remain resist
ant to digestion in lysosomal vesicles. Furthermore, it was suggested
that the hydrophobic region of peptides plays an important role in the
disruption of the endosomal membrane, which ca prevent the degradatio
n of DNA in lysosomal vesicles, When peptides do not have so strong me
mbrane-disruptive activity, but form aggregates which can be incorpora
ted by endocytosis, the transfection efficiency can be recovered by th
e addition of an endosome-disruptive peptide, (C) 1998 Academic Press.