CONFORMATIONAL-ANALYSIS OF HOMOCHIRAL AND HETEROCHIRAL DIPROLINES AS BETA-TURN-FORMING PEPTIDOMIMETICS - UNSUBSTITUTED AND SUBSTITUTED MODELS

The effect of replacing one of the proline residues in either unsubsti tuted homochiral or heterochiral diproline segments with either a 2- o r a 3-substituted prolyl residue on the allowed conformation of the di proline template has been examined. In heterochiral (L-D) diprolines, placement of a 2-methyl-D-proline residue in the i+2 position and plac ement 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 IT beta-turn conformation as that identified 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) d iproline peptide seems to promote a different conformation than that s een in the unsubstituted case, whereas the trans-3-methyl-D-proline re sidue seems to provide a stabilizing influence for the predicted type VI' beta-turn. The demonstrated ability of certain substituted diproli ne templates to adopt predictable conformations coupled with the devel opment of asymmetric synthetic routes to both 2- and S-substituted pro lyl residues capable of mimicking a variety of side chains should make these templates useful tools in designing specific turn mimics of bio logically active molecules. (C) Munksgaard 1997.