Stabilized structure of the presynaptic (Y2) receptor-specific neuropeptide Y analog N-acetyl[Leu-28Leu-31]NPY(24-36)

Abstract Neuropeptide Y analog N -acetyl[Leu-28, Leu-31]NPY(24-36)-amide binds specifically to prejunctional or Y 2 receptors acting to inhibit neurotransmitter release. The structure of this biologically active mutant was studied by two-dimensional proton nuclear magnetic resonance spectroscopy. Assignments of all backbone and side chain hydrogens were made by using totally correlated spectroscopy (TOCSY) experiments providing through-bond 1 H- 1 H connectivities, and nuclear Overhauser effect spectroscopy (NOESY), which provided through-space and sequential backbone connectivities. Structure analysis of the peptide was performed using distance geometry and dynamic simulated annealing revealing the presence of a helical structure exhibiting an amphiphilic character and slight constriction in the segment 24–29.