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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Teshome L AboyeJulio A Camarero

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.

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Citations

Oct 11, 2016·Expert Opinion on Drug Discovery·Andrew M White, David J Craik
Mar 2, 2017·Current Opinion in Chemical Biology·David J Craik, Junqiao Du
May 26, 2017·Chembiochem : a European Journal of Chemical Biology·Andrew Gould, Julio A Camarero
Feb 12, 2017·Angewandte Chemie·Eric ValeurAlleyn T Plowright
Apr 18, 2018·Nature Chemical Biology·Conan K Wang, David J Craik
Apr 24, 2019·Biomedicines·Julio A Camarero, Maria Jose Campbell
Jan 20, 2018·Physiological Reviews·Robson Augusto Souza SantosMaria Jose Campagnole-Santos
Mar 7, 2020·Journal of Peptide Science : an Official Publication of the European Peptide Society·Lovekesh MehtaSanjay Kumar
Jan 13, 2019·The Biochemical Journal·Dipankar ChaudhuriJulio A Camarero
Jun 30, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·E MazzioK F A Soliman
Oct 24, 2020·Chembiochem : a European Journal of Chemical Biology·Rafael González-CastroFabien Plisson
Nov 8, 2017·Bioorganic & Medicinal Chemistry Letters·Julio A Camarero
Jun 24, 2021·Chemistry : a European Journal·Rajasekaran GanesanJulio A Camarero
Aug 31, 2021·RSC Chemical Biology·Edin MuratspahićDavid J Craik

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Methods Mentioned

BETA
xenograft
fluorescence assay

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