{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kuhn KK"],"funding":["Deutsche Forschungsgemeinschaft"],"pagination":["3616-3631"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6044894"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2(7)"],"pubmed_abstract":["The cross-linked pentapeptides (2<i>R</i>,7<i>R</i>)-diaminooctanedioyl-bis(Tyr-Arg-Leu-Arg-Tyr-amide) ((2<i>R</i>,7<i>R</i>)-BVD-74D, (2<i>R</i>,7<i>R</i>)-<b>1</b>) and octanedioyl-bis(Tyr-Arg-Leu-Arg-Tyr-amide) (<b>2</b>) as well as the pentapeptide Ac-Tyr-Arg-Leu-Arg-Tyr-amide (<b>3</b>) were previously described as neuropeptide Y Y<sub>4</sub> receptor (Y<sub>4</sub>R) partial agonists. Here, we report on a series of analogues of (2<i>R</i>,7<i>R</i>)-<b>1</b> and <b>2</b> in which Arg<sup>2</sup>, Leu<sup>3</sup>, or Arg<sup>4</sup> were replaced by the respective aza-amino acids. The replacement of Arg<sup>2</sup> in <b>3</b> 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-<i>N</i><sup>ω</sup>-[(4-aminobutyl)aminocarbonyl]Arg-Leu-Arg-Tyr-amide (<b>35</b>), which was used as a precursor for a d-amino acid scan. The target compounds were investigated for Y<sub>4</sub>R functional activity in assays with complementary readouts: aequorin Ca<sup>2+</sup> and β-arrestin 1 or β-arrestin 2 assays. In contrast to the parent compounds, which are Y<sub>4</sub>R agonists, several ligands were able to suppress the effect elicited by the endogenous ligand pancreatic polypeptide and therefore represent a novel class of peptide Y<sub>4</sub>R antagonists."],"journal":["ACS omega"],"pubmed_title":["In Search of NPY Y<sub>4</sub>R Antagonists: Incorporation of Carbamoylated Arginine, Aza-Amino Acids, or d-Amino Acids into Oligopeptides Derived from the C-Termini of the Endogenous Agonists."],"pmcid":["PMC6044894"],"funding_grant_id":["GRK 1910","KE 1857/1-1"],"pubmed_authors":["Littmann T","Buschauer A","Dukorn S","Kuhn KK","Ozawa T","Tanaka M","Keller M","Bernhardt G"],"additional_accession":[]},"is_claimable":false,"name":"In Search of NPY Y<sub>4</sub>R Antagonists: Incorporation of Carbamoylated Arginine, Aza-Amino Acids, or d-Amino Acids into Oligopeptides Derived from the C-Termini of the Endogenous Agonists.","description":"The cross-linked pentapeptides (2<i>R</i>,7<i>R</i>)-diaminooctanedioyl-bis(Tyr-Arg-Leu-Arg-Tyr-amide) ((2<i>R</i>,7<i>R</i>)-BVD-74D, (2<i>R</i>,7<i>R</i>)-<b>1</b>) and octanedioyl-bis(Tyr-Arg-Leu-Arg-Tyr-amide) (<b>2</b>) as well as the pentapeptide Ac-Tyr-Arg-Leu-Arg-Tyr-amide (<b>3</b>) were previously described as neuropeptide Y Y<sub>4</sub> receptor (Y<sub>4</sub>R) partial agonists. Here, we report on a series of analogues of (2<i>R</i>,7<i>R</i>)-<b>1</b> and <b>2</b> in which Arg<sup>2</sup>, Leu<sup>3</sup>, or Arg<sup>4</sup> were replaced by the respective aza-amino acids. The replacement of Arg<sup>2</sup> in <b>3</b> 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-<i>N</i><sup>ω</sup>-[(4-aminobutyl)aminocarbonyl]Arg-Leu-Arg-Tyr-amide (<b>35</b>), which was used as a precursor for a d-amino acid scan. The target compounds were investigated for Y<sub>4</sub>R functional activity in assays with complementary readouts: aequorin Ca<sup>2+</sup> and β-arrestin 1 or β-arrestin 2 assays. In contrast to the parent compounds, which are Y<sub>4</sub>R agonists, several ligands were able to suppress the effect elicited by the endogenous ligand pancreatic polypeptide and therefore represent a novel class of peptide Y<sub>4</sub>R antagonists.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Jul","modification":"2025-05-29T20:28:22.863Z","creation":"2019-03-26T23:47:01Z"},"accession":"S-EPMC6044894","cross_references":{"pubmed":["30023699"],"doi":["10.1021/acsomega.7b00451"]}}