D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue.
Résumé
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.
Mots clés
Animals
Calcium Channels/chemistry
Circular Dichroism
Fluoresceins/chemistry
Magnetic Resonance Spectroscopy/methods
Microscopy, Confocal/methods
Peptide Hydrolases/chemistry
Peptides/*chemistry
Ryanodine/chemistry
Scorpion Venoms/*chemistry/pharmacology
Tetrazolium Salts/pharmacology
Thiazoles/pharmacology
Domaines
Neurosciences [q-bio.NC]
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Poillot-D-maurocalcine-2010-JBC-ver3-FIG-Auteur.pdf (574.22 Ko)
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inserm-00587800_edited.pdf (707.72 Ko)
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