Conformational analysis of homochiral and heterochiral diprolines as β‐turn‐forming peptidomimetics: unsubstituted and substituted models

This is the authors' abstract. We don't add key points for this paper.

The effect of replacing one of the proline residues in either unsubstituted homochiral or heterochiral diproline segments with either a 2- or a 3-substituted prolyl residue on the allowed conformational of the diproline template has been examined. In heterochiral (L-D) diprolines, placement of a 2-methyl-D-proline residue in the i + 2 position and placement of either a cis- or trans-3-methyl-L-proline residue in the i + 1 position results in substituted diproline peptides that adopt the same type II beta-turn conformation as that defined experimentally for the unsubstituted diproline peptides. In contrast, placement of a cis-3-methyl-D-proline residue in the i + 1 position of a homochiral (D-D) diproline peptide seems to promote a different conformation than that seen in the unsubstituted case, whereas the trans-3-methyl-D-proline residue seems to provide a stabilizing influence for the predicted type VI' beta-turn. The demonstrated ability of certain substituted diproline templates to adopt predictable conformations coupled with the development of asymmetric synthetic routes to both 2- and 3-substituted prolyl residues, capable of mimicking a variety of side chains should make these templates useful tools in designing specific turn mimics of biologically active molecules.