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

doi:10.1016/j.bmc.2006.05.019

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 journal › Article › peer-review

19 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 language	English
Pages (from-to)	5963-5972
Number of pages	10
Journal	Bioorganic and Medicinal Chemistry
Volume	14
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2006.05.019
Publication status	Published - 01 Sept 2006
Externally published	Yes

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

Access to Document

10.1016/j.bmc.2006.05.019

Cite this

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title = "Short pseudopeptides containing turn scaffolds with high AT2 receptor affinity",

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.",

keywords = "Angiotensin II, AT1 receptor, AT2 receptor, AT2 receptor agonist, Pseudopeptides, Turn scaffolds",

author = "Jennie Georgsson and Ulrika Rosenstr{\"o}m and Charlotta Wallinder and H{\'e}l{\`e}ne Beaudry and Bianca Plouffe and Gunnar Lindeberg and Milad Botros and Fred Nyberg and Anders Karl{\'e}n and Nicole Gallo-Payet and Anders Hallberg",

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doi = "10.1016/j.bmc.2006.05.019",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry",

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T1 - Short pseudopeptides containing turn scaffolds with high AT2 receptor affinity

AU - Georgsson, Jennie

AU - Rosenström, Ulrika

AU - Wallinder, Charlotta

AU - Beaudry, Hélène

AU - Plouffe, Bianca

AU - Lindeberg, Gunnar

AU - Botros, Milad

AU - Nyberg, Fred

AU - Karlén, Anders

AU - Gallo-Payet, Nicole

AU - Hallberg, Anders

PY - 2006/9/1

Y1 - 2006/9/1

N2 - 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.

AB - 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.

KW - Angiotensin II

KW - AT1 receptor

KW - AT2 receptor

KW - AT2 receptor agonist

KW - Pseudopeptides

KW - Turn scaffolds

UR - https://www.scopus.com/pages/publications/33746040078

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DO - 10.1016/j.bmc.2006.05.019

M3 - Article

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JO - Bioorganic and Medicinal Chemistry

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