STRUCTURAL CHARACTERIZATIONS OF NEUROPEPTIDE TYROSINE (NPY) AND ITS AGONIST ANALOG [AHX(5-17)]NPY BY NMR AND MOLECULAR MODELING

The structures of human NPY and of its centrally truncated agonist ana log [Ahx(5-17)]NPY have been investigated in DMSO-d(6) by two-dimensio nal NMR and by molecular modeling. For both peptides, a complete reson ance assignment was achieved and a large number (more than 200) of int er-residue NOE connectivities were observed, including long-range conn ectivities between the N- and C-terminal ends of the chain. Molecular models were calculated using NOE constraints by distance geometry, sim ulated annealing and conjugate gradient energy minimization, The resul ts indicate that both peptides are folded in the center of their chain , NPY adopting the hairpin shape, whereas the central portion of [Ahx( 5-17)]NPY is characterized by relatively large loops. In contrast to p revious models, practically no alpha-helical structure exists for thes e peptides under our conditions, but two beta-turns are found in NPY a nd one in [Ahx(5-17)]NPY. The proximity of the terminal ends could be the determinant factor for their activity. (C) Munksgaard 1995.