Phyllomedusin, an amphibian tachykinin decapeptide, has been shown to be selective for Neurokinin 1 receptor. Because the micelle-associated structure may be relevant to the Phyllomedusin-receptor interaction, the three-dimensional structure of the Phyllomedusin in aqueous and micellar environments has been studied by two-dimensional proton nuclear magnetic resonance (2D H-1 NMR spectroscopy) and distance geometry calculations. Sequence specific resonance assignments of protons have been made from correlation spectroscopy (TOCSY, DQF-COSY) and NOESY spectroscopy. The interproton distance constraints and dihedral angle constraints have been utilized to generate a family of structures using DYANA. The CD and NMR results show that, while in water Phyllomedusin prefers to be in an extended chain conformation, whereas in the presence of dodecylphosphocholine micelles, a membrane model system, a partial helical conformation is induced. Analysis of NMR data indicates that the global fold of Phyllomedusin can be explained in terms of equilibrium between 3(10)-helix and alpha-helix from residue 4 to 10. An extended highly flexible N-terminus displays some degree of order and a possible turn structure. A comparison between the conformational features of Phyllomedusin and different Neurokinin 1 receptor agonist indicates several common features in the distribution of hydrophobic and hydrophilic residues. The conformational similarities suggest that the molecules interact with receptor in an analogous manner. (C) 2009 Elsevier Inc. All rights reserved.