Folding trends in a flexible peptide: two-dimensional NMR study of deltorphin-I, a delta selective opioid heptapeptide.

Deltorphin-I, H-Tyr-(D)ala-Phe-Asp-Val-Val-Gly-NH2 and dermenkephalin, H-Tyr-(D)met-Phe-His-Leu-Met-Asp-NH2 are 2 members of small but growing family of D-amino acid containing opioid peptides isolated from the frog skin. Both peptides exhibit high affinity and selectivity for the delta-opioid receptor. Two-dimensional NMR study of deltorphin-I in DMSO-d6 revealed a close conformational homology with dermenkephalin. However, the temperature dependency of NOE correlations issued from Val5 and Val6 of deltorphin-I reflects a high intrinsic flexibility of the carboxyend. Whereas most of the JN alpha coupling constants and interresidue alpha N NOE effects were compatible with an extended structure, some sequential NOEs together with several medium and long range correlations involving Tyr1, Val6 and Asp4 may reflect an equilibrium mixture of extended and folded conformers in which the C- and the N-terminal parts of deltorphin-I are in close proximity. Finally, g- is the preferential conformer in the side chain of Phe3 in both deltorphin-I and dermenkephalin.