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Biochem. J. (2006) 399 (1–7) (Printed in Great Britain)
Review article
Cell-penetrating peptides and antimicrobial peptides: how different are they?
Sónia Troeira HENRIQUES, Manuel Nuno MELO and Miguel A. R. B. CASTANHO1
Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016 Lisbon, Portugal

Key words: antimicrobial peptide, cell-penetrating peptide, drug delivery, internalization, translocation mechanism.

Some cationic peptides, referred to as CPPs (cell-penetrating peptides), have the ability to translocate across biological membranes in a non-disruptive way and to overcome the impermeable nature of the cell membrane. They have been successfully used for drug delivery into mammalian cells; however, there is no consensus about the mechanism of cellular uptake. Both endocytic and non-endocytic pathways are supported by experimental evidence. The observation that some AMPs (antimicrobial peptides) can enter host cells without damaging their cytoplasmic membrane, as well as kill pathogenic agents, has also attracted attention. The capacity to translocate across the cell membrane has been reported for some of these AMPs. Like CPPs, AMPs are short and cationic sequences with a high affinity for membranes. Similarities between CPPs and AMPs prompted us to question if these two classes of peptides really belong to unrelated families. In this Review, a critical comparison of the mechanisms that underlie cellular uptake is undertaken. A reflection and a new perspective about CPPs and AMPs are presented.


Abbreviations used: AMP, antimicrobial peptide; CF, carboxyfluorescein; CPP, cell-penetrating peptide; NLS, nuclear localization signal; pAntp, Drosophila antennapedia transcription protein; SV40, simian virus 40; Tat, HIV-1 transcriptional activator protein.

1To whom correspondence should be addressed (email castanho@fc.ul.pt).


Received 19 July 2006/4 August 2006; accepted 4 August 2006

Published on the Internet 13 September 2006, doi:10.1042/BJ20061100


The Biochemical Society, London ©2006

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