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6
CONTENTS
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© 2002 by CRC Press LLC
Hydrophobic Membrane
Translocating Sequence
Peptides
Kristen Sadler, Yao-Zhong Lin, and James P. Tam
6.1 Introduction ..................................................................................................115
6.2 Signal Hypothesis ........................................................................................116
6.3 Hydrophobic Translocating Peptides Based on the Signal Sequence
h-Region .......................................................................................................117
6.3.1 Development of SN50 Peptide: kFGF MTS Linked
to NF-κB NLS .................................................................................117
6.3.2 Applications of SN50 Peptide .........................................................119
6.3.3 kFGF MTS Aids in Translocation of Other Cargoes......................119
6.3.4 Identification of Translocation Activity of Integrin β 3 h-Region....122
6.4 Mechanism of MTS Membrane Translocation............................................122
6.5 Methods for Attaching Cargo and Targeting Domains
to Translocating Peptides.............................................................................124
6.6 Cationic Translocating Peptides...................................................................127
6.7 Arginine–Proline-Rich Peptides as Translocating Peptides ........................129
6.8 Proline-Rich Peptides as Translocating Peptides ........................................130
6.9 Future Perspectives of Cell-Permeant Peptide Technology ........................130
References..............................................................................................................132
6.1 INTRODUCTION
Advances in genomics and proteomics have led to the design of a significant number
of therapeutic and diagnostic agents that target intracellular molecules. However,
the delivery of such agents to the cytoplasm and nucleus is impeded by the cell
membrane which is intrinsically impermeable to most peptides, proteins, and nucleic
acids. To overcome this barrier, invasive techniques such as microinjection, electroporation,
and application of pore-forming reagents have been used to introduce
biologically active tools such as antibodies, synthetic peptides, and peptidomimetics
into cells. 1-5 However, by their very nature, each of these techniques compromises the
structural and functional integrity of the living cell. Furthermore, these techniques,
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