Short pseudopeptides containing turn scaffolds with high AT2 receptor affinity

Jennie Georgsson, Ulrika Rosenström, Charlotta Wallinder, Hélène Beaudry, Bianca Plouffe, Gunnar Lindeberg, Milad Botros, Fred Nyberg, Anders Karlén, Nicole Gallo-Payet*, Anders Hallberg

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Two pentapeptides, Ac-Tyr-Ile-His-Pro-Phe/Ile, were synthesized and shown to have angiotensin II AT2 receptor affinity and agonistic activity. Based on these peptides, a new series of 13 pseudopeptides was synthesized via introduction of five different turn scaffolds replacing the Tyr-Ile amino acid residues. Pharmacological evaluation disclosed subnanomolar affinities for some of these compounds at the AT2 receptor. Substitution of Phe by Ile in this series of ligands enhanced the AT2 receptor affinity of all compounds. These results suggest that the C-terminal amino acid residues can be elaborated on to enhance the AT2 receptor affinity in truncated Ang II analogues.

Original languageEnglish
Pages (from-to)5963-5972
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number17
DOIs
Publication statusPublished - 01 Sep 2006
Externally publishedYes

Keywords

  • Angiotensin II
  • AT1 receptor
  • AT2 receptor
  • AT2 receptor agonist
  • Pseudopeptides
  • Turn scaffolds

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Georgsson, J., Rosenström, U., Wallinder, C., Beaudry, H., Plouffe, B., Lindeberg, G., Botros, M., Nyberg, F., Karlén, A., Gallo-Payet, N., & Hallberg, A. (2006). Short pseudopeptides containing turn scaffolds with high AT2 receptor affinity. Bioorganic and Medicinal Chemistry, 14(17), 5963-5972. https://doi.org/10.1016/j.bmc.2006.05.019