Pyrrolidine Ring Of Proline Research Articles

Conformational Mobility of the Pyrrolidine Ring of Proline in Peptides and Peptide Hormones as Manifest in Carbon 13 Spin-Lattice Relaxation Times

Abstract The spin-lattice relaxation times (T1) of carbon 13 in natural abundance were determined for proline, N-acetyl-prolineamide, 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 β, γ, and δ carbon atoms are appreciably more mobile than the α carbon atom, suggesting rapid interconversion between a number of ring-puckered forms. In melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) and its dimethylamido analog, the γ carbon atom has the greatest mobility, suggesting a rapid endo-exo interconversion at this position. In Gly-Pro and in acetyl-Pro-NH2, the cis and trans conformers of proline have very similar T1 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 Cβ and Cγ. In thyrotropin-releasing hormone (lGlu-His-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 [see PDF for equation] , lysine-vasopressin [see PDF for equation] , [Ile5]angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), and luteinizing hormone-releasing hormone ( lGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) all have proline in the trans conformation about the peptide bond, and the δ carbon atom has a mobility comparable to that of the α carbon atom. The latter reflects severe steric constraints at Cδ due to the neighboring residues. In oxytocin and angiotensin II, the β carbon atom is considerably more mobile than Cα or Cδ. In luteinizing hormonereleasing hormone, the proline ring apparently undergoes rapid interconversion between half-chair forms puckered at Cβ and Cγ, whereas in lysine-vasopressin, the mobility of Cγ is greatest.

THE DISSOCIATION CONSTANTS OF RACEMIC PROLINE AND CERTAIN RELATED COMPOUNDS

1. It has been experimentally shown that breaking of the pyrrolidine ring of proline by nitrous acid is not a factor of sufficient magnitude to account for the amino nitrogen which is usually found in proline preparations. 2. A method for the preparation of racemic proline is described. The product was found to be free from amino nitrogen. 3. The dissociation constants of racemic proline and of certain structurally related compounds were determined.