title: Conformation of neuropeptide Y receptor antagonists: structural implications in receptor selectivity.
abstract: 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.
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019295:Computational Biology; D003198:Computer Simulation; D030562:Databases, Protein; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D017476:Receptors, Neuropeptide Y; D012997:Solvents; D014867:Water; D014270:Trifluoroethanol