Kuhn, Kilian K. and Littmann, Timo and Dukorn, Stefanie and Tanaka, Miho and Keller, Max and Ozawa, Takeaki and Bernhardt, Gunther and Buschauer, Armin (2017) In Search of NPY Y4R Antagonists: Incorporation of Carbamoylated Arginine, Aza-Amino Acids, or D-Amino Acids into Oligopeptides Derived from the C-Termini of the Endogenous Agonists. ACS OMEGA, 2 (7). pp. 3616-3631. ISSN 2470-1343,
Full text not available from this repository. (Request a copy)Abstract
The cross-linked pentapeptides (2R, 7R)-diaminooctanedioyl- bis(Tyr-Arg-Leu-Arg-Tyr-amide) ((2R, 7R)BVD- 74D, (2R, 7R)-1) and octanedioyl-bis(Tyr-Arg-Leu-ArgTyr- amide) (2) as well as the pentapeptide Ac-Tyr-Arg-LeuArg- Tyr-amide (3) were previously described as neuropeptide Y Y-4 receptor (Y4R) partial agonists. Here, we report on a series of analogues of (2R, 7R)-1 and 2 in which Arg(2), Leu(3), or Arg(4) were replaced by the respective aza-amino acids. The replacement of Arg(2) in 3 with a carbamoylated arginine building block and the extension of the N-terminus by an additional arginine led to the high-affinity hexapeptide Ac-Arg-Tyr-N-omega-[(4-aminobutyl) aminocarbonyl] Arg-Leu-Arg-Tyr-amide (35), which was used as a precursor for a D-amino acid scan. The target compounds were investigated for Y4R functional activity in assays with complementary readouts: aequorin Ca2+ and beta-arrestin 1 or beta-arrestin 2 assays. In contrast to the parent compounds, which are Y4R agonists, several ligands were able to suppress the effect elicited by the endogenous ligand pancreatic polypeptide and therefore represent a novel class of peptide Y4R antagonists.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Y-1 RECEPTOR ANTAGONISTS; NEUROPEPTIDE-Y; HIGH-AFFINITY; PANCREATIC-POLYPEPTIDE; PEPTIDE; LIGANDS; ANALOGS; IDENTIFICATION; LUMINESCENCE; INHIBITOR; |
| 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: | 14 Dec 2018 13:16 |
| Last Modified: | 20 Feb 2019 07:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1577 |
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