Conformation of neuropeptide Y receptor antagonists: structural implications in receptor selectivity.

Two NPY analogue peptides, BVD10 (Ile-Asn-Pro-Ile-Tyr-Arg-Leu-Arg-Tyr-OMe) and BVD15 (Ile-Asn-Pro-Ile-Tyr-Arg-Leu-Arg-Tyr-NH(2)) were characterized conformationally by NMR, CD and molecular dynamics simulations. The two peptides exhibit different secondary structure characteristics in trifluoroethanol. BVD10 exhibits a structure with two consecutive beta-turns at Asn2-Pro3-Ile4-Tyr5 and Ile4-Tyr5-Arg6-Leu7. BVD15 exhibits a helical type of structure along with a beta-turn at Asn2-Pro3-Ile4-Tyr5. Molecular modeling studies suggested that the C-terminus Tyr9 is oriented in different directions in the two peptides. The difference in the structures of peptides observed may contribute to the Y(1) selectivity of BVD10 relative to BVD15.