Fluorescence study on the solution conformation to dynorphin in comparison of enkephalin.

Conformational parameters of the opioid peptides dynorphin and [Leu5] enkephalin in dilute aqueous solution (3 X 10(-5) M) were investigated by performing singlet-singlet energy transfer experiments with dynorphin and with the biologically active 4-tryptophan analogs of dynorphin-(1-13) and [Leu5] enkephalin at pH 5.5 and 8.0. Efficiencies of transfer of excitation energy from the phenol ring of tyrosine (donor) to the indole moiety of tryptophan (acceptor) were determined and average intramolecular Tyr-Trp distances were calculated on the basis of the Förster equation. The observed absence of energy transfer between Tyr1 and Trp14 of dynorphin indicates that the two fluorophores are at least 20 A apart and rules out a close proximity between the N- and C-terminal segments of the peptide. Evaluation of energy transfer in [Trp4] dynorphin-(1-13) resulted in an average intramolecular Tyr1-Trp4 distance of at least 15 A whereas the corresponding average distance in [Trp4, Leu5] enkephalin was found to be much shorter (10 A). It thus appears that in [Trp4] dynorphin-(1-13) the predominant conformation of the N-terminal tetrapeptide segment is almost completely extended, whereas in [Trp4, Leu5] enkephalin folded conformations of that same segment occur in a major proportion. This drastic conformational difference is of interest with regard to the different preferences of dynorphin and [Leu5] enkephalin for the various opiate receptor subclasses.