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

Molecules. 2016 Jan 26;21(2):152. doi: 10.3390/molecules21020152.

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)