THE RETRO-INVERSO FORM OF A HOMEOBOX-DERIVED SHORT PEPTIDE IS RAPIDLYINTERNALIZED BY CULTURED NEURONS - A NEW BASIS FOR AN EFFICIENT INTRACELLULAR DELIVERY SYSTEM

The capacity of a retro-inverso form of a 16-residue peptide from the Antennapedia homeodomain to be taken up by cultured neurones was teste d. Like its homologue made of L-amino acids, it ws rapidly internalise d and distributed throughout the cytoplasm and even the cell nucleus. The amount of retro-inverso peptide in cells after incubation in cultu re medium was 3.4 times that of the L-peptide form. With a cholesteryl moiety attached to the C-terminus to increase its lipophilicity, the retro-inverso peptide was internalised 8 times better than the L-form. The greater efficiency of the peptidomimetic is probably due to the r esistance to proteolytic degradation conferred by the D-amino acids, a s the sequence contains two sites sensitive to neuronal endoproteases. The peptide might be the basis for development of system for deliveri ng a variety of molecules into cells. (C) 1995 Academic Press, Inc.