The solution structure of human neuropeptide Y has been solved by conventional two-dimensional NMR techniques followed by distance-geometry and molecular-dynamics methods. Thc conformation obtained is composed of two short contiguous ol-helices comprising residues 15 -26 and 28 -35, linked by a hinge inducing a 100' angle. l h e first helix (15-26) is connected to a polyproline stretch (residues 1 -10) by a tight hairpin (residues 11 -14). The helices and thc polyprolinc stretch are packed together by hydrophobic interactions. This structure is related to that of the homologous avian pancreatic polypeptide and bovine pancreatic polypeptide. The C-and N-terminii, known to be involved in the biological activity for respectively the receptor binding and activation, are close together in space. The side chains of residues Arg33, Arg35 and Tyr36 on the one hand, and Tyrl and Pro2 on the other, form a continuous solvent-exposed surface of 4.9 nm2 which is supposed to interact with the receptor for neuropeptide Y Neuropeptide Y (NPY) is a 36-amino-acid neurotransmitter peptide (Fig. I), first isolated from porcine brain [l], but also found throughout the central and peripheral nervous system of many mammalian species, including man [2, 31. NPY has been identified within specific peptidergic neurons of central and autonomic nervous system. In the central nervous system, NPY stimulates food intake, produces cardiovascular depression, and inhibits the release of luteinizing hormone. In the periphery, it is a potent vasoconstrictor and a presynaptic inhibitor of neurotransmission (for a review, see [4]).NPY belongs to a family of homologous peptides, which includes peptide YY and the pancreatic polypeptides [3]. A member of this family, the avian pancreatic polypeptide (APP) has been crystallized and its structure determined by X-ray diffraction [5]. More recently, the structure of bovine pancreatic polypeptidc (BPP) has been determined by two-dimensional NMK in water [6]. Both APP and BPP have a verywell-defined C-terminal a-helix, involving residues 2 5 -32. This helix and the C-terminal region are joined by a turn. The rather ordered conformation of residues 4-8 is maintained by hydrophobic interaction between the helix and the Nterminal region. Both APP and BPP share a similar conformation.Models of NPY based on the crystal structure of the APP [5, 71 have been proposed [8,9]. Previous NMR studies as well as CD analysis [lo] have demonstrated that NPY, despite its small sizc and the absence of disulfide bridge, adopted a wellordered three-dimensional structure in water. However, the structure of the NPY dimer in solution has been described [ll]. This structure is composed of a helix consisting of residues 11 ~ 36 and an unstructured mobile N-terminal segment. This structure disagrees with those of APP and BPP.In this paper, we present the three-dimensional structure of huinan NPY in water as a monomer, obtained by distance geometry, restrained energy minimization and restrained simulated annealing. This structure is c...

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The 'H and 13C NMR spectra of amiodarone and several derivatives are reported and assigned. The hypothesis of an 0-trans to 0-cis conformational equilibrium in most of these molecules has been investigated by examining the 'H and I3C chemical shifts, and by NOE and LIS experiments, variable-temperature NMR and IR spectroscopy.The assumed 0-trans/O-cis equilibrium would be fast on the NMR time scale for amiodarone, which has no ortho substituents on the C-3 benzoyl substituent. However, in the 2',6'-dibromobenzoyl derivatives, separate 0-trans and 0-cis conformers are observed at room temperature in the NMR spectrum in the ratio of ca 60:40, favouring the 0-trans conformer. The coalescence temperatures and activation energies (A G$-) of the 2',6'-disubstituted compounds are obtained; the activation energy increases with the size of the ortho substituents but the conformer ratio remains unchanged. In contrast, removal of the C-2 butyl substituent on the benzofuran ring gives 100% of the 0-trans conformation.

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