Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶

Aneta Lukaszuk; Heidi Demaegdt; Isabelle Van den Eynde; Patrick Vanderheyden; Georges Vauquelin; Dirk Tourwé

doi:10.1002/psc.1365

Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶

Aneta Lukaszuk, Heidi Demaegdt, Isabelle Van den Eynde, Patrick Vanderheyden, Georges Vauquelin, Dirk Tourwé

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

The aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β-Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr¹, while only e-β-MePhe⁶ substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP-N or the AT₁ receptor. This indicates an important role of the orientation of the Phe⁶ for inducing selectivity. Pro⁵ replacement with 2-aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT₁ affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides.

Original language	English
Pages (from-to)	545-553
Number of pages	9
Journal	Journal of Peptide Science
Volume	17
Issue number	8
DOIs	https://doi.org/10.1002/psc.1365
Publication status	Published - Aug 2011

Keywords

Aminopeptidases
Angiotensin II
Animals
Biocatalysis
CHO Cells
Cell Membrane
Cells, Cultured
Cricetinae
Cricetulus
HEK293 Cells
Humans
Molecular Structure
Phenylalanine
Proline
Protein Conformation
Spectrophotometry, Atomic
Substrate Specificity
Tyrosine
Research Support, Non-U.S. Gov't

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10.1002/psc.1365

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title = "Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶",

abstract = "The aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β-Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr¹, while only e-β-MePhe⁶ substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP-N or the AT₁ receptor. This indicates an important role of the orientation of the Phe⁶ for inducing selectivity. Pro⁵ replacement with 2-aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT₁ affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides.",

keywords = "Aminopeptidases, Angiotensin II, Animals, Biocatalysis, CHO Cells, Cell Membrane, Cells, Cultured, Cricetinae, Cricetulus, HEK293 Cells, Humans, Molecular Structure, Phenylalanine, Proline, Protein Conformation, Spectrophotometry, Atomic, Substrate Specificity, Tyrosine, Research Support, Non-U.S. Gov't",

author = "Aneta Lukaszuk and Heidi Demaegdt and {Van den Eynde}, Isabelle and Patrick Vanderheyden and Georges Vauquelin and Dirk Tourw{\'e}",

note = "Copyright {\textcopyright} 2011 European Peptide Society and John Wiley & Sons, Ltd.",

year = "2011",

month = aug,

doi = "10.1002/psc.1365",

language = "English",

volume = "17",

pages = "545--553",

journal = "Journal of Peptide Science",

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T1 - Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶

AU - Lukaszuk, Aneta

AU - Demaegdt, Heidi

AU - Van den Eynde, Isabelle

AU - Vanderheyden, Patrick

AU - Vauquelin, Georges

AU - Tourwé, Dirk

PY - 2011/8

Y1 - 2011/8

N2 - The aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β-Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr¹, while only e-β-MePhe⁶ substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP-N or the AT₁ receptor. This indicates an important role of the orientation of the Phe⁶ for inducing selectivity. Pro⁵ replacement with 2-aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT₁ affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides.

AB - The aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β-Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr¹, while only e-β-MePhe⁶ substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP-N or the AT₁ receptor. This indicates an important role of the orientation of the Phe⁶ for inducing selectivity. Pro⁵ replacement with 2-aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT₁ affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides.

KW - Aminopeptidases

KW - Angiotensin II

KW - Animals

KW - Biocatalysis

KW - CHO Cells

KW - Cell Membrane

KW - Cells, Cultured

KW - Cricetinae

KW - Cricetulus

KW - HEK293 Cells

KW - Humans

KW - Molecular Structure

KW - Phenylalanine

KW - Proline

KW - Protein Conformation

KW - Spectrophotometry, Atomic

KW - Substrate Specificity

KW - Tyrosine

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/psc.1365

DO - 10.1002/psc.1365

M3 - Article

C2 - 21538707

VL - 17

SP - 545

EP - 553

JO - Journal of Peptide Science

JF - Journal of Peptide Science

SN - 1075-2617

IS - 8

ER -

Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶

Abstract

Keywords

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