Spacer length dependence on the efficiency of dimeric anionic peptides in gene transfer by glycosylated polylysine/plasmid complexes

Amphiphilic anionic peptides have been used to enhance the efficiency of tr ansfection by helping plasmids to escape from endosomes to the cytosol, It has been shown that efficiency of an eicosamers containing five glutamyl re sidues (E5), can be considerably enhanced either by transforming it into a dimer or by adding a tripeptide WYG in a C-terminal position (E5WYG). The d imerization of the peptide E5WYG leads to a more efficient tool when the di merization device includes the tripeptide WYG unit and a longer spacer arm made of Gly-beta Ala-beta Ala residues. but to a 10-fold less efficient too l when the dimerization device includes a shorter spacer, a glycyl residue. Both dimers are taken up by the calls to a similar extent. Both dimers see m to be surrounded similarly as far as the environmental pH is concerned. I n contrast, we found a correlation between the propensity of the peptides t o adopt a helical structure at neutral pH and the gene transfer efficiency.