Correlation of 15N and 13C relaxation data as a mobility probe for linear peptides. A theoretical and experimental study using enkephalins and related models

Abstract

The potential of 15N NMR relaxation data for conformational studies of small linear peptides is discussed, using 15N enriched enkephalin derivatives as follows: Tyr- ∗Gly- ∗Gly- ∗Phe, I; Boc-Tyr- ∗Gly- ∗Gly- ∗Phe-OCH 3, II; and Tyr- ∗Gly- ∗Gly- ∗Phe- ∗Leu, III. 15N relaxation data ( T 1/NOE) are interpreted in terms of molecular motion using the simplified two-spin system assumption for the NH bonds. In that way, two different approaches are developed: (i) the comparison of the temperature variation of T 1 for 15N and for 13C α which shows the occurrence of concerted motion for linked 15N and 13C, nuclei along the peptide backbone; (ii) the correlation of 15N relaxation data pairs ( T 1/NOE) by means of different molecular motion models to check which best fits with the experimental results. The isotropic overall motion model with internal libration appears most appropriate. The 15N “antisymmetric” T 1 obtained with an INEPT-derived pulse sequence provide useful parameters to study the conformational preferences in free linear peptides, because of the sensitivity of these quantities to intramolecular exchange processes which are distance dependent. All the results support folded conformations for the free peptides I and III and a random one for the diprotected peptide II.