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)|
|State||Published - Feb 2016|
Bibliographical noteFunding 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.).
© 2016 by the authors.
- MAS1 receptor