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 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.
Baures
P W
PW
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, USA.
Ojala
W H
WH
Gleason
W B
WB
Johnson
R L
RL
D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
C109519:3-methylproline; D010455:Peptides; C051624:2-methylproline; D011392:Proline