Design of a MCoTI-Based Cyclotide with Angiotensin (1-7)-Like Activity

• Published in: Molecules (Basel, Switzerland) Switzerland), 2016-01, Vol.21 (2), p.152-152
• Main Authors: Aboye, Teshome, Meeks, Christopher J, Majumder, Subhabrata, Shekhtman, Alexander, Rodgers, Kathleen, Camarero, Julio A
• Format: Article
• Language: English
• Subjects: angiotensin; Angiotensin AT1 receptors; Angiotensin I - chemistry; Angiotensin I - pharmacology; Animals; Biological activity; Cancer; Cell Survival - drug effects; Chemical synthesis; CHO Cells; Conformation; Cricetulus; cyclotide; Cyclotides - chemical synthesis; Cyclotides - chemistry; Cyclotides - pharmacology; Design; Endocrine system; Heart attacks; Humans; Lead compounds; Lung cancer; MAS1 receptor; Myocardial infarction; Myocardial Infarction - drug therapy; Neoplasms - drug therapy; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptides; Pharmacokinetics; Plant Proteins - chemistry; Polypeptides; Protein Conformation; Protein Folding; Protein Stability; Proteins; Proto-Oncogene Proteins - metabolism; Receptors, G-Protein-Coupled - metabolism
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21020152

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.