Page - (000304) - in Biomedical Chemistry: Current Trends and Developments

adopted by peptides as short as tripeptides (Motta, 2005). A γ-turn spans over three amino acid residues with a hydrogen bond between COi and NHi+2, resulting in the shape of a seven-membered ring. There are two types of γ-turns: the classic γ-turn with the i+1 residue side chain in an axial geometry and the inverse γ-turn with the side chain in an equatorial geometry (Table 3.3.1) (Matthews, 1972; Nemethy, 1972). Although the classic γ-turn was proposed first, it has been shown to be very rare and the inverse γ-turn is the significantly more common of the two (Milnerwhite, 1988). The classic γ-turn conformation causes reversal of the backbone direction and is mainly found in β-hairpin structures, as a tight turn, forming an antiparallel β-sheet structure. The inverse γ-turn can be found as backbone kinks and rarely causes reversal of the backbone direction (Milnerwhite, 1988). The information gained from the investigation of the bioactive conformation can provide indications regarding the presence of a turn structure in the bioactive conformation. Attempts to replace this part of the peptide with a turn mimetic would then be a rational step towards a peptide mimicking compound. However, how does one know if a particular organic scaffold indeed does mimic a turn, and in that case, which specific class of turns? One way of characterizing a potential turn mimicking moiety is to compare the geometry with experimental turn structures found in proteins (Claerhout, 2012; Rosenström, 2006; Whitby, 2011). The great abundance of protein 3D structures determined by X-ray crystallography in the Protein Data Bank (Berman, 2000) provides a good source of experimental protein secondary structures that can be used for this purpose. Using this method, both β- and γ-turn mimicking scaffolds have been characterized, which are exemplified below. β-Turn Mimicking Scaffold C Since turn mimicking moieties usually have reduced peptidic character and thus do not have a straightforward atom-to-atom match to the peptide, the phi and psi dihedral angles used to classify β-turns can be difficult to use for classifying β-turn mimetics. Instead, another rational classification approach is to compare the geometries of the mimicking