Tachykinins elicit a wide and complex array of biological responses, such as, stimulation of extra-vascular smooth muscle, powerful vasodilation, hypertensive action, activation of immune system, regulation of pain transmission and neurogenic inflammation. Both the aqueous and the lipid-induced structure of NK2 - selective tachykinin agonists have been characterized by CD spectropolarimetryand two-dimensional proton nuclear magnetic resonance (2D ¹H-NMR) spectroscopy. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The distance constraints obtained from the NMR data have been utilized to generate a family of structures, which have been refined using restrained energy minimization and dynamics. Our data show that, in aqueous medium, Neurokinin A and its analogues are in extended chain conformations. In the presence of perdeuterated dodecylphosphocholine (DPC) micelles, a membrane model system, helical conformation is induced in the central core and C-terminal region. N-terminus though less defined also displays some degree of order and a possible turn structure. An attempt has been made to correlate the observed conformational differences to the binding ability and biological activity of various neurokinin-2 selective agonists.

Keywords: 2D-NMR spectroscopy, Bioactive peptides, Tachykinins, NK-2 agonist, Lipid induced structure.