CELLULAR UPTAKE OF AN ALPHA-HELICAL AMPHIPATHIC MODEL PEPTIDE WITH THE POTENTIAL TO DELIVER POLAR COMPOUNDS INTO THE CELL INTERIOR NON-ENDOCYTICALLY

Evidence that multiple, probably non-endocytic mechanisms are involved in the uptake into mammalian cells of the alpha-helical amphipathic m odel peptide FLUOS-KLALKLALKALKAALKLA-NH2 (I) is presented. Extensive cellular uptake of N-terminally GC-elongated derivatives of I, conjuga ted by disufide bridges to differently charged peptides, indicated tha t I-like model peptides might serve as vectors for intracellular deliv ery of polar bioactive compounds. The mode of the cellular internaliza tion of I comprising energy-, temperature- pH- and ion-dependent as we ll as -independent processes suggests analogy to that displayed by sma ll unstructured peptides reported previously (Oehlke et al., Biochim. Biophys. Acta 1330 (1997) 50-60). The uptake behavior of I also showed analogy to that of several protein-derived helical peptide sequences, recently found to be capable of efficiently carrying tagged oligonucl eotides and peptides directly into the cytosol of mammalian cells (Der ossi et al., J. Biol. Chem. 269 (1994) 10444-10450; Lin et al., J. Bio l. Chem. 270 (1995) 14255-14258; Fawell et al., proc. Natl. Acad. Sci. USA 91 (1994) 663-668; Chaloin ct al., Biochemistry 36 (1997) 11179-1 1187; Vives et al., J. Biol. Chem., 272 (1997) 16010-16017). (C) 1998 Elsevier Science B.V. All rights reserved.