Structure-Activity Relationships of Neuropeptide Y

Neuropeptide Y (NPY) represents a 36-peptide amide playing a crucial role in the regulation of blood pressure. Highly active lead structures for the development of new anti-hypertonic drugs were discovered using synthetic cyclic analogs of NPY. NPY analogs and peptide mimetics have been screened in Y 1 and Y 2 receptor binding assays and biological testing systems. The spatial structure of NPY was investigated by spectroscopic techniques (2D-NMR, CD) and molecular dynamic simulations.

1. A. G. Beck-Sickinger, W. Gaida, G. Schnorrenberg, R. Lang, and G. Jung (1990).
Neuropeptide Y: Identification of the Binding Site, Int. J. Pept. Prot. Res. 36, 522-530.

2. A. G. Beck-Sickinger, G. Jung, W. Gaida, H. Köppen, G. Schnorrenberg, and R. Lang (1990).
Structure-activity Relationships of C-terminal Neuropeptide Y Segments and Analogues composed of NPY 1-4 linked to NPY 25-36, Eur. J. Biochem. 194, 449-456.

3. A.G. Beck-Sickinger, E. Grouzmann, E. Hoffmann, W. Gaida, E.G. Van Meir, B. Waeber, and G. Jung (1992).
A Novel Cyclic Analog of Neuropeptide Y Specific for the Y ₂ -Receptor, Eur. J. Biochem. 206, 957-964.

4. G. Jung, A. G. Beck-Sickinger, H. Dürr, W. Gaida, and G. Schnorrenberg (1991).
alpha-Helical Small Molecular Size Analogues of Neuropeptide Y: Structure-Activity-Relationships, Biopolymers 31, 613-619.

5. M. C. Michel, W. Gaida, A. G. Beck-Sickinger, H. A. Wieland, H. Doods, H. Dürr, G. Jung, and G. Schnorrenberg (1992).
Further Characterization of Neuropeptide Y Receptor Subtypes Using Centrally Truncated Analogs of Neuropeptide Y: Evidence for Subtype-Differentiating Effects on Affinity and Intrinsic Efficancy, Mol. Pharmacol. 42, 642-648.

6. D. F. Mierke, H. Dürr, H. Kessler, and G. Jung (1992).
Neuropeptide Y: Optimized Solid Phase Synthesis and Conformational Analysis in Trifluoroethanol, Eur. J. Biochem. 206, 39-48.

7. A.G. Beck-Sickinger, H. Dürr, W. Gaida, and G. Jung (1992).
Characterization of the Binding Site of Neuropeptide Y to the Rabbit Kidney Receptor Using Multiple Peptide Synthesis, Biochem. Soc. Trans. 20, 847-850.

8. A. G. Beck-Sickinger, H. Köppen, E. Hoffmann, W. Gaida, and G. Jung (1993).
Cyclopeptide Analogs for Characterization of the Neuropeptide Y Y ₂ -Receptor, J. Receptor Research 13, 215-228.

9. A. G. Beck-Sickinger, E. Hoffmann, W. Gaida, E. Grouzmann, H. Dürr, and G. Jung (1993).
Novel Y ₂ -Selective, Reduced-Size Agonists of Neuropeptide Y, Bioorg. Med. Chem. Lett. 3, 937-942.

10. A. G. Beck-Sickinger, E. Hoffmann, K. Paulini, H.-U. Reisig, K.-D. Willim, and G. Jung (1994).
High Affinity Analogues of Neuropeptide Y Containing Conformationally Restricted Non-proteinogenic Amino Acids, Biochem. Soc. Trans. 22, 145-149.

11. A.G. Beck-Sickinger, H.A. Wieland, H. Wittneben, K.-D. Willim, K. Rudolf, and G. Jung (1994).
Complete L-Alanine Scan of Neuropeptide Y Reveals Ligands Binding to Y ₁ and Y ₂ Receptors with Distinguished Conformations, Eur. J. Biochem. 225, 947-958.

12. A.G. Beck-Sickinger and G. Jung (1995).
Structure-Activity Relationships of Neuropeptide Y Analogues with Respect to Y ₁ and Y ₂ Receptors, Biopolymers (Peptide Science) 37, 123-142.

13. L.J.M. Cross, A.G. Beck-Sickinger, M. Bienert, W. Gaida, G. Jung, E. Krause, and M. Ennis (1996)
Structure Activity Studies of Mast Cell Activation and Hypotension Induced by Neuropeptide Y (NPY), Centrally Truncated and C-terminal NPY Analogues. Brit. J. Pharmacol. 117, 325-332.

14. S. Hoffmann, B. Rist, G. Videnov, G. Jung and A.G. Beck-Sickinger (1996)
Structure-Affinity Studies of C-Terminally Modified Analogs of Neuropeptide Y led to a Novel Class of Peptidic Y ₁ Receptor Antagonist, Regulatory Peptides 65, 61-70.

cojinfo@uni-tuebingen.de(cojinfo@uni-tuebingen.de) - July 23, 1997