Maurocalcine-derivatives as biotechnological tools for the penetration of cell-impermeable compounds. Maurocalcine-derivatives as biotechnological tools for the penetration of cell-impermeable compounds: Technological value of a scorpion toxin

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Ram, Narendra | Jaumain, Emilie | Ronjat, Michel | Pirollet, Fabienne | de Waard, Michel

Edité par CCSD ; Editora UFMG Belo Horizonte, Brazil -

Maurocalcine is a unique toxin in that its natural pharmacological target in vivo, the ryanodine receptor, is localized inside cells and not at the cell surface as commonly observed for most toxins. According to the membrane topology of the ryanodine receptor, the binding site of maurocalcine is localized within the cytoplasm. Application of maurocalcine to myotubes in culture induces calcium release via the ryanodine receptor within seconds indicating that the peptide reaches its binding site via a rapid and efficient diffusion through the plasma membrane. Analysis of the maurocalcine amino-acid sequence indicates that it is a heavily positively charged peptide, a property shared with many cell-penetrating peptides. A closer examination of the 3D structure of maurocalcine further illustrates that most of its positively charged residues are located on one face of the molecule according to a distribution that resembles that seen in Tat and penetratin, two cell penetrating peptides. Along with its unique cell penetrating properties, maurocalcine has also the ability to act as a vector for the intracellular delivery of various many cargo molecules or nanoobjects. Many key cell penetration properties of maurocalcine have been defined using a biotinylated version of the peptide that was coupled to a fluorescent streptavidin. Various structure-function strategies have been developed to isolate new maurocalcine analogues presenting the characteristic cell penetration properties without the undesired pharmacological activity. Examples of research and technological applications will be presented in which maurocalcine may prove a powerful delivery vector. By its amazing diversity of potential applications, this peptide opens a new trend of research in the toxin field.

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