Membrane Crossover by Cell-Penetrating Peptides: Kinetics and Mechanisms – From Model to Cell Membrane Perturbation by Permeant Peptides - Intracellular Delivery: Fundamentals and Applications - page 180

HS Heparan Sulphate

HSPG Heparan Sulphate ProteoGlycans

ITC Isothermal Titration Calorimetry

LUV Large Unilamellar Vesicle

MAP Membrane Active Peptide

NBD Nitrobenzo-2-oxa-1,3-diazole

NMR Nuclear Magnetic Resonance Spectroscopy

PEP-1 hepatite C virus related peptide, SGSWLRDVWDWICTVLTDFK-

TWLQSKLDYKD-NH 2

P/L ratio peptide over lipid ratio

Transportan galanin/mastoparan chimeric peptide, GWTLNSAGYLLGKINLK-

ALAALAKKIL-NH 2

Tat Trans Activator of Transcription protein

Tat(46-58) Tat derived peptide, GRKKRRQRRRPQ-NH 2

1 Introduction

Cellular signaling mechanisms in plants and animals include homeoprotein
transduction, which is particularly important in developmental and physiological
processes (Tassetto et al. 2005 ; Brunet et al. 2007 ). Homeoproteins have an important
paracrine function, being secreted by and internalized into neighbored cells (Prochiantz
and Joliot 2003 ; Joliot and Prochiantz 2008 ). Specialized peptide domains that are
endowed with the property of membrane translocation have been identified in numer-
ous different proteins (Lindgren et al. 2000 ; Prochiantz 2008 ). These peptides are
grouped under the generic term of cell-penetrating peptides (CPPs) or, when they are
derived from proteins, such as the Antennapedia homeoprotein or Tat transcription
factors, protein transduction domains (PTD) (Hansen et al. 2008 ). These peptides have
the ability to convey into cells conjugated cargo molecules that can give a positive
biological or imaging read out of the intracellular localization of the peptide (Dietz
and Bähr 2004 ; El-Andaloussi et al. 2004 ; Morris et al. 2008 ).

2 Amino Acid Composition of Cell-Penetrating Peptides

Dozens of different cell-penetrating peptides have now been reported, which derive
from natural protein sequences or have been rationally designed (Hansen et al.
2008 ). Those peptides are indeed basic and/or amphipathic with a length of 10-20
amino acids. Some of these permeant peptides are pure basic sequences such as
oligoarginine (R8, R9) (Futaki et al. 2001 ; Wender et al. 2001 ; Nakase et al. 2004 )
or Tat(48-59) (GRKKRRQRRRPQ) peptides (Weeks et al. 1995 ; Vives et al. 1997 )
when others are more hydrophobic such as transportan (WTLNSAGYLLGKINL-
KAKAAKAKKIL).