Kuhn, Kilian K. and Ertl, Thomas and Dukorn, Stefanie and Keller, Max and Bernhardt, Guenther and Reiser, Oliver and Buschauer, Armin (2016) High Affinity Agonists of the Neuropeptide Y (NPY) Y-4 Receptor Derived from the C-Terminal Pentapeptide of Human Pancreatic Polypeptide (hPP): Synthesis, Stereochemical Discrimination, and Radiolabeling. JOURNAL OF MEDICINAL CHEMISTRY, 59 (13). pp. 6045-6058. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
The diastereomeric mixture of D/L-2,7-diaminooctanedioyl-bis(YRLRY-NH2) (BVD-74D, 2) was described in the literature as a high affinity Y-4 receptor agonist. Here we report on the synthesis and pharmacological characterization of the pure diastereomers (2R,7R)- and (2S,7S)-2 and a series of homo- and heterodimeric analogues in which octanedioic acid was used as an achiral linker. To investigate the role of the Arg residues, one or two arginines were replaced by Ala. Moreover, N-omega-(6-aminohexylaminocarbonyl)Arg was introduced as an arginine replacement (17) (2R,7R)-2 was superior to (2S,7S)-2 in binding and functional cellular assays and equipotent with 17. [H-3]Propionylation of one amino group in the linker of (2R,7R)-2 or at the primary amino group in 17 resulted in high affinity Y4R radioligands ([H-3]-(2R,7R)-10, [H-3]18) with subnanomolar K-d values.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACID-DERIVATIVES; ANTAGONISTS; LIGANDS; FAMILY; METATHESIS; POTENT; HYDROGENATION; LUMINESCENCE; EXPRESSION; PEPTIDES; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2019 12:11 |
| Last Modified: | 29 Mar 2019 12:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3629 |
Actions (login required)
 |
View Item |
