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:
MAS1 receptor; angiotensin; cyclotide.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Angiotensin I / chemistry
-
Angiotensin I / pharmacology
-
Animals
-
CHO Cells
-
Cell Survival / drug effects
-
Cricetulus
-
Cyclotides / chemical synthesis*
-
Cyclotides / chemistry
-
Cyclotides / pharmacology*
-
Humans
-
Myocardial Infarction / drug therapy
-
Neoplasms / drug therapy
-
Peptide Fragments / chemistry
-
Peptide Fragments / pharmacology
-
Plant Proteins / chemistry*
-
Protein Conformation
-
Protein Folding
-
Protein Stability
-
Proto-Oncogene Mas
-
Proto-Oncogene Proteins / metabolism*
-
Receptors, G-Protein-Coupled / metabolism*
Substances
-
Cyclotides
-
MAS1 protein, human
-
MCoTI-I protein, Momordica cochinchinensis
-
Peptide Fragments
-
Plant Proteins
-
Proto-Oncogene Mas
-
Proto-Oncogene Proteins
-
Receptors, G-Protein-Coupled
-
Angiotensin I
-
angiotensin I (1-7)