Maurocalcine

Maurocalcine (MCa) is a protein, 33 Amino acid residues in length, isolated from the venom of the scorpion Maurus palmatus, which belongs to the family Chactidae, first characterized in 2000.

This structural feature allows CPPs to cross biological membranes in a receptor- or transporter-independent manner through a mechanism called translocation.

[3]  MCa is similar to CPP sequences because MCa is a small peptide, it has a net positive charge, it enters many cell types, it enters in an efficient manner and at low concentration, the translocation is a fast process that is energy-independent, and it can carry a cargo molecule.

The specific mutations were K8A, K19A, K20A, K22A, R23A, R24A and the effects of MCa and its mutants on RyR1 incorporated into artificial lipid bilayers and on elementary calcium release events (ECRE) in rat and frog skeletal muscle fibers were observed.

This reveals that the effect of the mutations of basic amino acids to neutral amino acids cannot be solely attributed to the change of the net electrical charge of the peptide since mutations that were distant to the cluster but produced the same change in net electrical charge had relatively minor effects.

[3] The toxin complex efficiently penetrated into various cell types without requiring metabolic energy or implicating an endocytosis mechanism.

Doxorubicin, a common cancer therapeutic, has been covalently coupled to an analogue of maurocalcine on drug-sensitive or drug-resistant cell lines MCF7 and MDA-MB 231.

Figure 1: The Inhibitor Cystine Knot motif is shown. A compact disulfide-bond core with the following three pairs: Cys3-Cys17, Cys10-Cys21, and Cys16-Cys32.
Figure 2: MCa has a dipole moment with a basic-rich surface including the residues Lys19, Lys20, Lys22, Arg23, Arg24, and Arg3 without any acidic residue. The opposite surface contains four acidic residues Asp2, Glu12, Asp15, and Glu29.