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 Y-1 and Y-2, in the present study the syntheses and conformational analyses of two C-terminal segments, NPY(1836) and NPY(1336), are described. The results obtained by CD measurements, two-dimensional NMR spectros copy and a conformational refinement of the NMR-derived structure by molecular mechanics simulations 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(1836) are in agreement with the prerequisites proposed for Y-2 receptor binding of that segment.