From noxiustoxin to Shiva-3, a peptide toxic to the sporogonic development of Plasmodium berghei.

Abstract : This communication reviews shortly the main structural and functional characteristics of Noxiustoxin, a 39 amino acid residue peptide, maintained closely packed by three-disulfide bridges and its effects on excitable membranes. Shiva-3, a cecropin like-peptide composed of 38 amino acid residues is also briefly reviewed. Its design and synthesis was made possible by the expertise gained through the work previously performed with Noxiustoxin. One of the most prominent functional characteristics of Shiva-3 is the toxic effect upon the sporogonic development of Plasmodium berghei (responsible for a murine version of malaria). A synthetic Shiva-3 gene was constructed by recursive polymerase-chain reaction (PCR) methodology and expressed using the vector pGEX2T as a hybrid protein between the glutathione-S-transferase at the N-terminal and Shiva-3 in the C-terminal part of the hybrid. The recombinant protein kills bacteria and Plasmodium berghei. The future aim of this work is to produce a transgenic mosquito that carries the message for synthesis and excretion of Shiva-3 and similar peptides, in the midgut of mosquitoes, in an attempt to control the spreading of human malaria.