Résumé
Serine, threonine-derived (4S)-oxazolidine-4-carboxylic acid, and cysteine-derived (4R)-thiazolidinecar-boxylic acid, denoted pseudo-proline (Xaa[ΨR1,R 2pro]), serve as structure disrupting, solubilizing building blocks inpeptide synthesis. Variation of the 2-C substituents within the heterocyclic system results in different physicochemicaland conformational properties. NMR studies of a series of pseudo-proline (ΨPro)-containing peptides reveal apronounced effect of the 2-C substituents upon the cis to trans ratio of the adjacent amide bond in solution. 2-Cunsubstituted systems show a preference similar to that of the proline residue for the trans form, whereas 2,2-dimethylated derivatives adopt the cis amide conformation in high content. For 2-monosubstituted ΨPro, the cis-trans distribution depends on the 2-C chirality. For the 2-(S)-diastereoisomer, both forms are similarly populated insolution, whereas the 2-(R)-epimer adopts preferentially the trans form. The results are supported by conformationalenergy calculations and suggest that, by tailoring the degree of substitution, pseudo-prolines may serve as a temporaryproline mimetic or as a hinge in peptide backbones.