STRUCTURAL INFORMATION ON A CECROPIN-LIKE SYNTHETIC PEPTIDE, SHIVA-3 TOXIC TO THE SPOROGONIC DEVELOPMENT OF PLASMODIUM-BERGHEI

This study is a contribution towards the understanding of the mode of action of Shiva-3 and more generally that of cecropin-like peptides. S tructural information on Shiva-3 (a cecropin-like synthetic peptide) i n water and in a membrane-mimicking environment (trifluoroethanol alco hol, SDS) were obtained using analytical centrifugation, CD and NMR sp ectroscopies. A total of 20 converged structures were retained on the basis of 197 non-redundant experimental constraints, includings 166 di stance constraints from the nuclear Overhauser effect measurements and 31 dihedral angle restraints derived from the purged COSY experiments . Some results obtained in presence of SDS are also presented. The tox ic effects of the peptides obtained by cleavage (trypsin and lysine-C hydrolysis) of Shiva-3 on Escherichia coil and on Plasmodium berghei s porogonic stages are reported. Biological effects are discussed in rel ation to the calculated structure. The antiparasite activity and the l ow mosquito toxicity of Shiva-3 make this peptide a good candidate for genetic transformation of mosquito vectors which warrants further stu dies aimed at the improvement of the molecule.