D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue
| Autor: | Poillot, Cathy, Dridi, Kaouthar, Bichraoui, Hicham, Pêcher, Julien, Alphonse, Sébastien, Douzi, Badreddine, Ronjat, Michel, Darbon, Hervé, de Waard, Michel |
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| Přispěvatelé: | Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Canepari, Marco |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
MESH: Fluoresceins
MESH: Peptide Hydrolases MESH: Ryanodine Ryanodine/chemistry MESH: Thiazoles MESH: Cricetinae CHO Cells MESH: Circular Dichroism Cricetulus MESH: Scorpion Venoms MESH: Cricetulus MESH: CHO Cells Cricetinae Thiazoles/pharmacology Animals MESH: Microscopy Confocal MESH: Animals Peptides/*chemistry [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Magnetic Resonance Spectroscopy/methods Microscopy Confocal/methods MESH: Peptides MESH: Magnetic Resonance Spectroscopy Calcium Channels/chemistry Circular Dichroism Cell Membrane/metabolism Peptide Hydrolases/chemistry Scorpion Venoms/*chemistry/pharmacology MESH: Tetrazolium Salts MESH: Calcium Channels [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Fluoresceins/chemistry Tetrazolium Salts/pharmacology MESH: Cell Membrane |
| Zdroj: | Journal of Biological Chemistry 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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