FROM NOXIUSTOXIN TO SHIVA-3, A PEPTIDE TOXIC TO THE SPOROGONIC DEVELOPMENT OF PLASMODIUM-BERGHEI

This communication reviews shortly the main structural and functional characteristics of Noxiustoxin, a 39 amino acid residue peptide, maint ained closely packed by three-disulfide bridges and its effects on exc itable membranes. Shiva-3, a cecropin like-peptide composed of 38 amin o acid residues is also briefly reviewed. Its design and synthesis was made possible by the expertise gained through the work previously per formed with Noxiustoxin. One of the most prominent functional characte ristics 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-termina l and Shiva-3 in the C-terminal part of the hybrid. The recombinant pr otein kills bacteria and Plasmodium berghei. The future aim of this wo rk is to produce a transgenic mosquito that carries the message for sy nthesis and excretion of Shiva-3 and similar peptides, in the midgut o f mosquitoes, in an attempt to control the spreading of human malaria. (C) 1998 Elsevier Science Ltd. All rights reserved.