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218 Cell-Penetrating Peptides: Processes and Applications
E
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FIGURE 9.10 (continued)
pAntp (inner leaflet charge: -0.04)
Total Restraints (kJ/mol Å 2 )
Mass Center Penetration (A)
leaflet, penetratin, the second helix, of the Antennapedia homeodomain, its first
helix, and the entire homeodomain are predicted to penetrate, at least partially, in
the membrane. Therefore, we suggest that the charge gradient within biological
membranes would constitute an important factor for driving translocation of penetratins
and homeodomains through biological membranes.
These results are not contradictory with, but rather complete, models built up
according to previously published experimental data. 17,68,69 These models suggested
formation of inverted micelle with negatively charged phospholipids during the
crossing of biological membranes. Indeed the presence of PL – , may constitute the
first step enabling penetratin to interact with the membrane, to be followed by
formation of inverted micelles. This new computer-based method should be very
useful for screening and designing new peptide derivatives with cell-permeant potential.
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