The Antennapedia peptide penetratin translocates across lipid bilayers - the first direct observation

The potential use of polypeptides and oligonucleotides for therapeutical pu rposes has been questioned because of their inherently poor cellular uptake . However, the 16-mer oligopeptide penetratin, derived from the homeodomain of Antennapedia, has been reported to enter cells readily via a non-endocy totic and receptor- and transporter-independent pathway, even when conjugat ed to large hydrophilic molecules. We here present the first study where pe netratin is shown to traverse a pure lipid bilayer. The results support the idea that the uptake mechanism involves only the interaction of the peptid e with the membrane lipids. Furthermore, we conclude that the translocation does not involve pore formation. (C) 2000 Federation of European Biochemic al Societies. Published by Elsevier Science B.V. All rights reserved.