ABSTRACT
A large number of peptides, such as cell-penetrating peptides (CPPs), which exhibit
their biological activities at the cell membrane are hydrosoluble. Because the task of
solving the structure of membrane-embedded compounds is still difficult, it is
tempting to deduce the membrane form from that identified for the water-soluble
one. However, in spite of the recent progress in the identification of peptide and
protein structures, the mechanisms and the structural consequences involved in the
transfer of peptides from one of these media to the other is still not well understood.
Clearly, several different situations are encountered going from a conservation of the
overall structure to a major refolding. In fact, this concerns the initial and final steps
of the transfer, and in the case of a water to membrane transfer an additional step,
although transitory, has to be examined and concerns the adsorption at the
water-membrane interface.1 Another factor which plays a crucial role in the
possible lipid-induced conformational changes lies in the chemical structure of
the peptides and thus of their hydrophobic profile and flexibility providing the
possibility for some sequences to strongly interact with the membrane components.
Membrane-active peptides are generally built of hydrophilic and hydrophobic
sequences which generate amphipathic properties. When in solution in aqueous
media, they fold such as to expose their hydrophilic residues toward the solvent and
thus will often adopt a globular form which can be roughly compared to a micelle.
This form is stabilized by the cohesion forces between the hydrophobic domains,
and when they are transferred into an organic medium, the tendency will be reversed
such as to anchor the hydrophilic and hydrophobic parts in the polar and nonpolar
media, respectively. Hence, the structural versatility of such peptides is a direct
consequence of their amphipathic character and the structural changes by interfacial
uptake are known as superficial unfolding.
