Ring Conformational Aspects of Proline and Hydroxyproline. High Conformational Purity of Pro in DKP's and Hydantoïns.

Abstract

Abstract1H‐nmr literature data for Pro and trans‐Hyp peptides (acyclic and cyclic) are reviewed and complemented with data including some new compounds (diketopiperazines and hydantoins). In both acyclic and cyclic derivatives, the hydroxy proline ring possesses a unique and highly homogenous conformation λ− or λE form) which is gradually changed into a ‐form when ø‐values become for L‐residues more negative than ‐40°. Correspondingly, the Pro ring possesses more flexibility especially in the acyclic derivatives where an admixture of different forms is present. The situation becomes biased in cyclic derivatives, although the intrinsically higher mobility of the ring prevails somewhat when compared to Hyp. Also the nature of the major populations in the pseudorotational path of the five‐membered ring is somewhat more sensitive in Pro towards changes in ø. Thus, for ø ∼O° mainly a libration in the ßE‐γE region is present, while the γE form becomes the major one when ø ∼ −40° (L‐residues). For still lower values of ø the pseudorotational phase angle is displaced resulting in a αE form for ø ∼ −100° as the extreme limit. Relative shifts in the 1H nmr spectra for the methylene ring protons may serve as a qualitative estimation of the buckle of DKP‐rings and therefore also for cis‐trans assignments. The shift anisotropy caused by the unique orientation of the aromatic side chain in c/D‐Phe‐L‐Pro/ corroborates the findings for the ring conformations of both the flattened DKP‐boat and of the γ−‐form of Pro.