Conformational analysis of neuropeptide Y segments by CD, NMR spectroscopy and restrained molecular dynamics

Neuropeptide Y (NPY), a peptide amide comprising 36 residue has been shown to act as a potent vasoconstrictor. In order to shed light on the structural requirements for the biological activities with respect to the different prerequisites for affinity to the NPY receptor subtypes Y1 and Y2, in the present study the syntheses and conformational analyses of two C-terminal segments, NPY(18-36) and NPY(13-36), are described. The results obtained by CD measurements, two-dimensional NMR spectroscopy and a conformational refinement of the NMR-derived structure by molecular mechanics stimulations support the findings of previously published structure-activity relationship studies for biologically active and selective compounds. In particular, the alpha-helical conformation as well as an appropriate exposure of the side chains of the critical C-terminal dipeptide within NPY(18-36) are in agreement with the prerequisites proposed for Y2 receptor binding of that segment.