CONFORMATIONAL-ANALYSIS BY NMR AND DISTANCE-GEOMETRY TECHNIQUES OF DELTORPHIN ANALOGS

To identify the peptide conformation that is preferentially recognized by the receptor, we have synthetized by solid-phase method a series o f deltorphin I analogs with increasing selectivity for delta- and mu-o pioid receptor. Structure-selectivity relationship of these peptides w ere evaluated on the basis of receptor-binding properties and conforma tional features, computed by two-dimensional NMR spectra and distance- geometry techniques. These compounds in solution are present with a la rge number of conformers with no defined secondary structural elements . The analysis of the average properties of these compounds indicate t he presence of some distinct conformational preferences that can be re lated to the observed opioid receptor selectivities. Selectivity for t he delta- and mu-opioid receptors can be ascribed to the spatial arran gement of the aromatic moieties. In addition, substitutions in positio n 2 and 4 are important for the correct arrangement and must be taken into account in the design of delta-opioid receptor-selective ligands.