CONSTRUCTION OF SECONDARY STRUCTURAL MODULES

The remarkable range of chemical capability that evolution has elicited from protein suggest that it might be possible to design analogous capabilities into synthetic polypeptides that fold into compact and specific conformations. The first step in foldamer design must therefore be to identify new backbones with well-defined secondary structural preferences. Well-defined in this case means that the conformational preference should be displayed in solution by oligomers of modest length. Considering the 3D structure of the globular proteins here mentioned the almost unique packing is affected by a combination of steric interactions (excluded volume effects) and energetic stabilization (hydrophobic, polar and charge interactions). The proportion by which these interactions contribute to the overall stability is unknown but several studies suggest that steric and hydrophobic interactions are of primary importance. To access the relative influence of hydrogen bonding and hydrophobic interactions on ?-structure formation one must be able to parse their contribution separately. Peptide models have proved extremely valuable in probing the relationship between local sequence information and folded conformation in the absence of the tertiary interactions found in the native state of proteins, allowing intrinsic secondary structure propensities to be investigated in isolation. With this rationale in mind, we have chosen to investigate bioactive sequences containing hydrophobic residues, highly predisposed to assume ?-turn conformation.