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3 Transportans
Margus Pooga, Mattias Hällbrink, and Ülo Langel
CONTENTS
3.1 Introduction ....................................................................................................53
3.2 The Discovery of Transportan .......................................................................53
3.3 Cell Penetration of Transportan.....................................................................55
3.4 Properties of Transportan...............................................................................57
3.5 Structure–Activity Relationship of Transportan............................................58
3.6 Transportan as a Delivery Vector...................................................................59
3.6.1 Delivery of Peptides...........................................................................59
3.6.2 Delivery of PNA ................................................................................60
3.6.3 Delivery of Proteins ...........................................................................61
3.7 Methodological Considerations .....................................................................66
3.7.1 Cargo–CPP Conjugation Strategies ...................................................66
3.7.2 Disulfide Heterodimers ......................................................................66
3.7.3 Conjugation of Transportan to Proteins ............................................66
3.8 Structural Organization of Transportan .........................................................67
Acknowledgments....................................................................................................69
References................................................................................................................69
3.1 INTRODUCTION
The first discovered cell-penetrating peptides (CPPs) were derived from naturally
occurring proteins like the Antennapedia homeodomain of Drosophila, 1 Tat of HIV-
1, 2 and VP22 of HSV, 3 followed soon by designed chimeric peptides like MTS-
NLS, 4 transportan, 5 and model peptides. 6 Numerous analogues of these CPPs have
now been designed and synthesized, giving rise to families of respective peptides.
Both classes of CPPs, protein-derived and designed or combined, have been vastly
expanded by new peptides and derivatives. In this chapter we summarize the discovery,
properties, and application of the cell-penetrating peptide transportan and
its analogues.
3.2 THE DISCOVERY OF TRANSPORTAN
The predecessor of transportan, galparan, comprises a fragment of the neuropeptide
galanin (1–13) and the wasp venom peptide mastoparan. 7 (Table 3.1) It was designed
under a program aimed at creating galanin receptor ligands by using a chimeric
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© 2002 by CRC Press LLC
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