The retro-inverso form of a homeobox-derived short peptide is rapidly internalised by cultured neurones: 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 tested. Like its homologue made of L-amino acids, it was rapidly internalised and distributed throughout the cytoplasm and even the cell nucleus. The amount of retro-inverso peptide in cells after incubation in culture 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 resistance to proteolytic degradation conferred by the D-amino acids, as the sequence contains two sites sensitive to neuronal endoproteases. The peptide might be the basis for development of system for delivering a variety of molecules into cells.
Brugidou
J
J
Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 9008-INSERM U249-Université Montpellier I, France.
Legrand
C
C
Méry
J
J
Rabié
A
A
D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001692:Biological Transport; D001710:Biotin; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004337:Drug Carriers; D004622:Embryo, Mammalian; D018398:Homeodomain Proteins; D007532:Isoleucine; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism
D051943:Antennapedia Homeodomain Protein; D004268:DNA-Binding Proteins; D004337:Drug Carriers; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D010455:Peptides; D014157:Transcription Factors; D007532:Isoleucine; D001710:Biotin