S. D. Samarasinghe*, A. Balasubramaniam and M. E. Johnson Pages 151 - 158 ( 8 )
NPY is regarded as the most common peptide in the central and peripheral nervous systems and heart of many mammalian species including man. It has been found to perform critical regulatory functions in behavior, control of the cardiovascular system, memory processing etc. Development of highly selective and potent antagonists will allow better understanding of the pathological and physiological roles of NPY. In the process of designing potent receptor antagonists, which are essential in detailed studies of structure function relationships, NMR has played a major role in determining the solution structure of NPY and its analogs. Sequential proton NMR assignments have been made using several two dimensional techniques, COSY, DQFCOSY, HOHAHA, NOESY and ROESY. NMR has served as a complementary technique to X-ray since solid state studies do not necessarily always provide the correct picture of molecular conformation in solution, particularly for small flexible peptides. NPY consists of an a-helix domain (residues 15- 35) with a hinge at position 27 and a polyproline stretch (residues 1--10) connected by a tight hairpin (residues 11-14). NMR has provided critical information in demonstrating formation of NPY dimers in aqueous media. Based on these results, recent designs have shown that high affinity analogs can be developed through C-terminal analogs dimerized with disulfide or lactam bridges. This review surveys NMR studies of NPY and its analogs with particular reference to the use of NMR data in molecular modeling of the solution structure.