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

32 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

Access to Document

10.3390/molecules21020152

Cite this

@article{25ff6bceeacd4051af5e1dde75218faa,

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.",

year = "2016",

month = feb,

doi = "10.3390/molecules21020152",

language = "English (US)",

volume = "21",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "2",

}

TY - JOUR

T1 - Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity

AU - Aboye, Teshome

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

UR - http://www.scopus.com/inward/record.url?scp=84963668266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963668266&partnerID=8YFLogxK

U2 - 10.3390/molecules21020152

DO - 10.3390/molecules21020152

M3 - Article

C2 - 26821010

AN - SCOPUS:84963668266

SN - 1420-3049

VL - 21

JO - Molecules

JF - Molecules

IS - 2

M1 - 152

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this