D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue.. D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue.: Cell Penetrating D-Maurocalcine Peptide

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Poillot, Cathy | Dridi, Kaouthar | Bichraoui, Hicham | Pêcher, Julien | Alphonse, Sébastien | Douzi, Badreddine | Ronjat, Michel | Darbon, Hervé | de Waard, Michel

Edité par CCSD ; American Society for Biochemistry and Molecular Biology -

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.

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