Helical conformation amino acid amphiphiles

By inserting appropriate amino acid side chains (e.g., hydrophilic and hydrophobic), it is feasible to construct amphiphilic helices (with two faces that possess different properties). The conformational strategy should take into account the parameters typical of each of the two helices, in particular that 1) The a-helix (Fig. la) is characterized by a fractional number of amino acids per turn (=3.5) and consequently its smallest repeat (i.e., the shortest main-chain length that brings two side chains exactly one on top of the other) is a heptad (7 residues) and 2) in the 3io-helix (Fig. lb), which has an integer number of amino acids per turn (=3.0), a triplet of residues selected carefully will produce the expected amphiphiUcity. 

The largest group of facial amphiphilic peptides consists of the alpha-helical peptides. Facial amphiphilic alpha helices, often referred to as amphipathic alpha helices, are not amphiphilic in their random coil conformation and their amphiphilicity is not directly obvious from then-sequence. However, folding of the peptide into its preferred secondary structure, leads to the formation of an alpha helix, of which the hydrophilic amino acids occupy one face and the hydrophobic amino acids are located at the other face. Alpha-helical peptides have a periodicity of 3.6 amino acid residues per turn, and because of this, for two turns, roughly every third and seventh amino acids are on the same face of the alpha helix. In order to make a helix amphiphilic, the sequence of amino acids should alternate between hydrophobic and hydrophilic every three to four residues, which becomes more clear in a helical wheel representation (Figure 3). An example of such a facial amphiphilic alpha helix is magainin 2, a 23 amino acid antibiotic peptide. Studies have shown that magainin... 

In order to examine the possibility of this speculation, an approach using synthetic peptides was made [10]. Three kinds of peptides (H, S, and R) with 16 amino acid residues were synthesized, and their secondary structure and surface properties were investigated to clarify the effects of conformational amphiphilicity. The amino acid compositions of the three peptides were the same (8 Leu and 8 Glu residues), but their sequences were different. The helical wheel structure of peptide H is shown in Fig. 2e [5], As shown in this structure, peptide H was designed to form an amphiphilic a-helix, whereas the other peptides were designed not to show such amphiphilicity, even when... 

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