ryanodine and thiazolyl-blue

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.

Topics: Animals; Calcium Channels; Cell Membrane; CHO Cells; Circular Dichroism; Cricetinae; Cricetulus; Fluoresceins; Magnetic Resonance Spectroscopy; Microscopy, Confocal; Peptide Hydrolases; Peptides; Ryanodine; Scorpion Venoms; Tetrazolium Salts; Thiazoles