Conformational mobility of the pyrrolidine ring of proline in peptides and peptide hormones as manifest in carbon 13 spin-lattice relaxation times.

The spin-lattice relaxation times (Tl) of carbon 13 in natural abundance were determined for proline, N-acetylprolineamide, glycylproline, cyclo(triprolyl), and a series of proline-containing peptide hormones. The data are interpreted in terms of rapid interconversion of proline between various ring-puckered forms. The nature of the puckering depends upon the type of group attached to proline. In proline, the 0, y, and 6 carbon atoms are appreciably more mobile than the Q! carbon atom, suggesting rapid interconversion between a number of ring-puckered forms. In melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NHt) and its dimethylamido analog, the y carbon atom has the greatest mobility, suggesting a rapid endo-exo interconversion at this position. In Gly-Pro and in acetyl-Pro-NHr, the cis and trans conformers of proline have very similar 2’1 values, indicating very little dependence of the dynamic proline ring conformation on the conformation at the peptide bond; in both isomers, the proline ring interconverts rapidly between half-chair conformers puckered at C/3 and Cy. In thyrotropin-releasing hormone ( <GluHis-Pro-NH2), the proline ring conformation is similar to that in Gly-Pro, and independent of the state of ionization of the histidine residue. Oxytocin (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-