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2 Penetratins
CONTENTS
0-8493-1141-1/02/$0.00+$1.50
© 2002 by CRC Press LLC
Edmond Dupont, Alain Joliot,
and Alain Prochiantz
2.1 Introduction ....................................................................................................24
2.2 Homeoprotein-Derived Peptidic Vectors .......................................................24
2.2.1 The Antennapedia Homeodomain .....................................................24
2.2.2 The Penetratin-1 Peptide....................................................................25
2.3 How Do Penetratin Peptides Cross Cellular Membranes? ...........................26
2.3.1 Influence of Structural Parameters on Peptide Translocation...........26
2.3.1.1 Chirality ..............................................................................27
2.3.1.2 Helicity................................................................................27
2.3.1.3 Amphiphilicity ....................................................................27
2.3.1.4 Sequence Length.................................................................27
2.3.1.5 Relative Importance of Each Individual Residue ..............28
2.3.2 Peptide–Lipid Interactions .................................................................28
2.3.3 Proposed Model of Penetratin Internalization...................................29
2.4 Delivery of Hydrophilic Cargoes into Live Cells
with Penetratin Vectors ..................................................................................31
2.4.1 Principles of Cargo–Vector Linkage..................................................31
2.4.2 Vectorization with AntpHD ...............................................................31
2.4.2.1 AntpHD-Mediated Internalization of Oligonucleotides.....31
2.4.2.2 AntpHD-Mediated Internalization of Polypeptides ...........34
2.4.2.2.1 In Vitro ..............................................................34
2.4.2.2.2 In Vivo...............................................................34
2.4.3 Vectorization with Penetratin Peptide, In Vitro Studies ....................35
2.4.3.1 Oligonucleotide and Oligopeptide Delivery.......................35
2.4.3.1.1 Cell Death and Cell Cycle Regulation.............35
2.4.3.1.2 Regulation of Signal Transduction...................37
2.4.3.2 Delivery of Peptide Nucleic Acids (PNAs)........................37
2.4.3.3 Delivery of Entire Proteins.................................................38
2.4.3.4 Chemical Drug Delivery.....................................................38
2.4.4 In Vivo Internalization with Penetratin-Derived Vectors...................39
2.4.4.1 Immune System ..................................................................39
2.4.4.2 Delivery of Peptides in Blood Vessels ...............................39
2.4.4.3 Direct Perfusion Inside the Central Nervous System ........39
2.4.4.4 The Blood–Brain Barrier....................................................39
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