Conformation of the tripeptide Cbz-Pro-Leu-Trp-OBzl(CF3)2 deduced from two-dimensional 1H-NMR and conformational energy calculations is related to its affinity for NK1-receptor

Chemical modifications of dual NK1/NK2 ligand Cbz-Gly-Leu-Trp-OBzl(CF3)(2) (1) enabled us to create a high NK, selective ligand Cbz-Pro-Leu-Trp-OBzl(CF3)(2) (2). A determination of the conformational behavior of tripeptide 2 in solution is described. The 1D and 2D H-1-NMR techniques (COSY and ROESY) were used to assign resonances. Observed interproton distance restraints were considered to characterize conformational behavior. Spectral data indicate that tripeptide 2 presents a rigidified structure in DMSO stabilized by H-bond in two gamma -turns. Agreement with experimental data was obtained by averaging the H-1-NMR parameters over several combinations of low-energy conformations. Copyright (C) 2001 European Peptide Society and John Wiley & Sons, Ltd.