Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity

Teshome Aboye; Christopher J. Meeks; Subhabrata Majumder; Alexander Shekhtman; Kathleen Rodgers; Julio A. Camarero

doi:10.3390/molecules21020152

Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity

Teshome Aboye, Christopher J. Meeks, Subhabrata Majumder, Alexander Shekhtman, Kathleen Rodgers, Julio A. Camarero

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

40 Scopus citations

Abstract

We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction.

Original language	English (US)
Article number	152
Journal	Molecules
Volume	21
Issue number	2
DOIs	https://doi.org/10.3390/molecules21020152
State	Published - Feb 2016
Externally published	Yes

Keywords

Angiotensin
Cyclotide
MAS1 receptor

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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10.3390/molecules21020152

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title = "Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity",

abstract = "We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction.",

keywords = "Angiotensin, Cyclotide, MAS1 receptor",

author = "Teshome Aboye and Meeks, {Christopher J.} and Subhabrata Majumder and Alexander Shekhtman and Kathleen Rodgers and Camarero, {Julio A.}",

note = "Funding Information: Acknowledgments: This work was supported by National Institutes of Health Research Grants R01-GM090323 (J.A.C.), R01-GM113363 (J.A.C.) and R01-GM085006 (A.S.). Publisher Copyright: {\textcopyright} 2016 by the authors.",

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doi = "10.3390/molecules21020152",

language = "English (US)",

volume = "21",

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AU - Meeks, Christopher J.

AU - Majumder, Subhabrata

AU - Shekhtman, Alexander

AU - Rodgers, Kathleen

AU - Camarero, Julio A.

N1 - Funding Information: Acknowledgments: This work was supported by National Institutes of Health Research Grants R01-GM090323 (J.A.C.), R01-GM113363 (J.A.C.) and R01-GM085006 (A.S.). Publisher Copyright: © 2016 by the authors.

PY - 2016/2

Y1 - 2016/2

N2 - We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction.

AB - We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction.

KW - Angiotensin

KW - Cyclotide

KW - MAS1 receptor

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Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity

Abstract

Keywords

ASJC Scopus subject areas

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