STRUCTURE OF THE PRESYNAPTIC (Y-2) RECEPTOR-SPECIFIC NEUROPEPTIDE-Y ANALOG ANA-NPY

Neuropeptide Y analog ANA-NPY or [Leu-17, Gln-19, Ala-20, Ala-23, Leu-28, Leu-31]NPY(13-36)-amide binds to postjunctional or Y-1 receptors to raise blood pressure and to prejunctional or Y-2 receptors to inhibit neurotransmitter release. ANA-NPY affects Y-2 receptors in the same way as intact NPY but exhibits Ear less potent effects on Y-1 receptors. The structure of ANA-NPY was examined using two-dimensional proton nuclear magnetic resonance spectroscopy. Complete assignment of all backbone and side chain hydrogens was accomplished with totally correlated spectroscopy (TOCSY) experiments providing through-bond H-1-H-1 connectivities, and nuclear Overhauser effect spectroscopy (NOESY), providing the through-space and sequential backbone connectivities. The tertiary solution structure of the peptide was performed using distance geometry and dynamic simulated annealing. ANA-NPY exhibits a helical structure with strong amphipathic character with a bend around Glu-24 indicating that the C-terminal segment 25-35 forms a single alpha-helical motif.