STABILIZED STRUCTURE OF THE PRESYNAPTIC (Y-2) RECEPTOR-SPECIFIC NEUROPEPTIDE-Y ANALOG N-ACETYL[LEU-28,LEU-31]NPY(24-36)

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