Structure-activity relationships of neuropeptide Y (NPY)

Neuropeptide Y (NPY) is a 36-peptide amide, which inter alia plays a central role in blood pressure regulation. Highly active, potential lead structures for the development of drugs were shortened and cyclised analogues of NPY. Y1 and Y2-receptor binding assays and biological assays with the synthetic NPY analogues were carried out. Spectroscopic conformational investigations (CD, 2D-NMR) and molecular dynamics simulation supported the SAR studies.

Molecular dynamics simulation of neuropeptide Y (model for Y2-receptor affinity)

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,
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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 Y2-receptor, Eur. J. Biochem. 206, 957-964.

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 Efficacy, Mol. Pharmacol. 42, 642-648.

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.

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, Biochern. Soc. Trans. 20, 847-850.

A G. Beck-Sickinger, E. Hoffmann, K Paulini, H.-D. 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.

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 Y1 and Y2 Receptors with Distinguished Conformations, Eur. J. Biochem. 225,947-958.

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.

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