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.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089-9121, USA. aboye@usc.edu.
authors.forename: Teshome
authors.initials: T
authors.lastname: Aboye
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089-9121, USA. meeksc@usc.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Meeks
authors.affiliation: Department of Chemistry, State University of New York, Albany, NY 12222, USA. smajumder@albany.edu.
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Majumder
authors.affiliation: Department of Chemistry, State University of New York, Albany, NY 12222, USA. ashekhtman@albany.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shekhtman
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089-9121, USA. krodgers@usc.edu.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Rodgers
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089-9121, USA. jcamarer@usc.edu.|Department of Chemistry, University of Southern California, Los Angeles, CA 90089-9121, USA. jcamarer@usc.edu.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Camarero
mesh_terms: D000803:Angiotensin I / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D047169:Cyclotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010940:Plant Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D047169:Cyclotides; C000715470:MAS1 protein, human; C409922:MCoTI-I protein, Momordica cochinchinensis; D010446:Peptide Fragments; D010940:Plant Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: MAS1 receptor; angiotensin; cyclotide
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