Deletion Analogues Of Transportan

Several shorter analogues of the cell penetrating peptide, transportan, have been
synthesized in order to define the regions of the sequence, which are responsible
for the membrane translocation property of the peptide. Penetration of the
peptides into Bowes melanoma cells and the influence on GTPase activity in Rin
m5F cellular membranes have been tested. The experimental data on cell
penetration have been compared with molecular modeling of insertion of peptides
into biological membranes. Omission of six amino acids from the N-terminus did
not significantly impair the cell penetration of the peptide while deletions at
the C-terminus or in the middle of the transportan sequence decreased or
abolished the cellular uptake. Most transportan analogues exert an inhibitory
effect on GTPase activity. Molecular modeling shows that insertion of the
transportan analogues into the membrane differs for different peptides. Probably
the length of the peptide as well as the location of aromatic and positively
charged residues have major impact on the orientation of peptides in the
membranes and thereby influence the cellular penetration. In summary, we have
designed and characterized several novel short transportan analogues with similar
cellular translocation properties to the parent peptide, but with reduced
undesired cellular activity.