D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue
| Autor: | Hicham Bichraoui, Sébastien Alphonse, Badreddine Douzi, Kaouthar Dridi, Cathy Poillot, Michel De Waard, Julien Pecher, Hervé Darbon, Michel Ronjat |
|---|---|
| Přispěvatelé: | Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Smartox Biotechnologies, Université Joseph Fourier - Grenoble 1 (UJF)-FLORALIS, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Magnetic Resonance Spectroscopy
medicine.medical_treatment MESH: Ryanodine Tetrazolium Salts MESH: Cricetinae Peptide Biochemistry MESH: Circular Dichroism Cell membrane MESH: Scorpion Venoms MESH: Cricetulus Cricetinae MESH: Microscopy Confocal MESH: Animals Magnetic Resonance Spectroscopy/methods chemistry.chemical_classification 0303 health sciences Microscopy Confocal Microscopy Confocal/methods Ryanodine MESH: Peptides Circular Dichroism Chinese hamster ovary cell 030302 biochemistry & molecular biology Scorpion Venoms/*chemistry/pharmacology Biological activity MESH: Tetrazolium Salts Fluoresceins medicine.anatomical_structure MESH: Calcium Channels Maurocalcine [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Fluoresceins/chemistry MESH: Fluoresceins MESH: Peptide Hydrolases Ryanodine/chemistry Scorpion Venoms MESH: Thiazoles CHO Cells Biology 03 medical and health sciences Cricetulus In vivo MESH: CHO Cells Membrane Biology Thiazoles/pharmacology medicine Animals Peptides/*chemistry Molecular Biology 030304 developmental biology Protease MESH: Magnetic Resonance Spectroscopy Calcium Channels/chemistry Cell Membrane/metabolism Cell Membrane Peptide Hydrolases/chemistry Cell Biology Thiazoles chemistry Cell-penetrating peptide Calcium Channels Tetrazolium Salts/pharmacology Peptides Peptide Hydrolases MESH: Cell Membrane |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (44), pp.34168-80. ⟨10.1074/jbc.M110.104919⟩ Journal of Biological Chemistry, 2010, 285 (44), pp.34168-80. ⟨10.1074/jbc.M110.104919⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M110.104919⟩ |
| Popis: | International audience; Maurocalcine has been the first demonstrated animal toxin acting as a cell-penetrating peptide. Although it possesses competitive advantages, its use as a cell-penetrating peptide (CPP) requires that analogues be developed that lack its characteristic pharmacological activity on ryanodine-sensitive calcium channels without affecting its cell-penetrating and vector efficiencies. Here, we present the synthesis, three-dimensional (1)H NMR structure, and activity of D-maurocalcine. We demonstrate that it possesses all of the desired features for an excellent CPP: preserved structure, lack of pharmacological action, conserved vector properties, and absence of cell toxicity. This is the first report of a folded/oxidized animal toxin in its D-diastereomer conformation for use as a CPP. The protease resistance of this new peptide analogue, combined with its efficient cell penetration at concentrations devoid of cell toxicity, suggests that D-maurocalcine should be an excellent vector for in vivo applications. |
| Databáze: | OpenAIRE |
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