Molecular conformations of dermorphin: A unique non-nervous tissue mu-agonist

The molecular conformations of dermorphin, Tyr(1)-D-Ala(2) - Phe(3) - Gly(4 ) - Tyr(5) - Pro(6) - Ser(7)-NH2, are derived from FT-IR, Raman, CD, and 2D NMR spectroscopic studies in aqueous solution. Segawa et al. (1994,1995) h ave recently reported NMR studies of dermorphin in aqueous solution from wh ich a folded conformation has been postulated. The folded conformation of d ermorphin suggested by this study is characterized by a stacking of the aro matic side chains of Tyr(1) and Phe(3). This appears to be critical to the pharmacological profile of dermorphin. The experimentally derived conformat ion bears partial resemblance to the low energy conformations predicted by molecular mechanics calculations. The proposed conformational model and its possible relevance to the mu-agonist activity of dermorphin are discussed.