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crc press - E-Lib FK UWKS

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236 Cell-Penetrating Peptides: Processes and Applications<br />

TABLE 10.2<br />

Sequences of Selected Membrane-Active Peptides<br />

Name Sequence Translocation Lytic/Pore<br />

Melittin GIGAVLKVLTTGLPALISWIKRKRQQ-NH 2 yes yes 33<br />

Magainin 2 GIGKFLHSAKKFGKAFVGEIMNS yes yes 47,48<br />

Mastoparan X INWKGIAAMAKKLL-NH 2 yes yes 47<br />

Buforin 2 TRSSRAGLQWPVGRVHRLLRK yes no 54<br />

Note: Positively charged residues are underlined.<br />

Among the other CPPs included in Table 10.1, the Tat peptide had been discussed<br />

in terms of an amphipathic α-helix, 46 whereas two NLS-chimera seem to adopt βstructures<br />

with phospholipid vesicles, irrespective of the surface charge. 12,13<br />

10.7 POSSIBLE EFFECTS OF PEPTIDES ON MEMBRANES:<br />

COMPARISON WITH OTHER TYPES<br />

OF MEMBRANE-INTERACTING PEPTIDES<br />

There is a vast amount of literature on membrane interactions and membrane effects<br />

by bioactive peptides. Biological effects have been compared with studies of interactions<br />

and structures in membrane model systems. In contrast to the more hydrophobic<br />

peptides, sometimes of an integral type, the highly amphipathic and watersoluble<br />

small peptides are more unpredictable in their biophysical behavior. Here<br />

we will only mention a few examples of the latter type of peptide and discuss various<br />

biological and physico-chemical effects defined for some peptides that may be<br />

relevant for understanding CPPs. We have selected the antimicrobial peptides, a<br />

widespread and much studied class of peptides. 47-51<br />

Antimicrobial and toxic peptides from various sources, exemplified by magainin<br />

(frog skin), melittin (bee venom), and mastoparan X (wasp venom), are examples<br />

of pore-forming peptides which, under certain conditions, cause the cell membrane<br />

to disrupt and lead to lysis of the cell. The sequences and a summary of their<br />

characteristic effects on biological membranes are shown in Table 10.2.<br />

The overall view is that these peptides exert their cytotoxicity by permeabilizing<br />

cell membranes. The positively charged peptides are particularly toxic to bacterial<br />

membranes, which are negatively charged overall. A transmembrane potential (negative<br />

inside) has been found to increase the ability of peptides to induce cell lysis. The exterior<br />

side of the plasma membrane of mammalian cells is more neutral in charge (zwitterionic)<br />

and hence should have a lower affinity for the peptide. This is generally given as<br />

an explanation for the lower biological activity with mammalian cells as compared to<br />

bacterial cells, and thus the selective toxicity and the rescue of the host cells.<br />

Amphiphaticity and aggregational states have been much discussed for the<br />

antimicrobial peptides, mostly in terms of (helical) secondary structures and membrane<br />

topology. The mechanisms of action have been suggested to include dynamic

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