SOLUTION STRUCTURE OF NEUROPEPTIDE TYROSINE-13-36, A Y2 RECEPTOR AGONIST, AS DETERMINED BY NMR

The three-dimensional structure of neuropeptide tyrosine (NPY) 13-36, a specific Y2 receptor agonist, has been investigated by two-dimension al H-1-NMR spectroscopy in solution. Analysis of the double-quantum-fi ltered correlation spectroscopy (DQFCOSY), total correlation spectrosc opy (TOCSY) and nuclear Overhauser enhancement spectroscopy (NOESY) sp ectra provided a complete assignment of the proton signals. The interp roton connectivities observed in the NOESY spectra comprised 166 intra residue and 95 interresidue distance ranges which were used as constra ints for molecular modeling by distance geometry, simulated annealing and energy minimization. The optimal structures are characterized by a helical C-terminal fragment Leu30-Tyr36 and a wide loop from Leu17 to Ser22. The structure of NPY 13-36 is analogous to the structure of NP Y under the same solvent conditions. Comparison with other reported Y2 agonists suggests that the helical Leu30-Try36 fragment is the most c ritical for activity.