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. Structural information on Shiva-3 (a cecropin-like synthetic peptide) in water and in a membrane-mimicking environment (trifluoroethanol alcohol, SDS) were obtained using analytical centrifugation, CD and NMR spectroscopies. A total of 20 converged structures were retained on the basis of 197 non-redundant experimental constraints, including 166 distance 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 toxic effects of the peptides obtained by cleavage (trypsin and lysine-C hydrolysis) of Shiva-3 on Escherichia coli and on Plasmodium berghei sporogonic stages are reported. Biological effects are discussed in relation to the calculated structure. The antiparasite activity and the low mosquito toxicity of Shiva-3 make this peptide a good candidate for genetic transformation of mosquito vectors which warrants further studies aimed at the improvement of the molecule.
Boisbouvier
J
J
Laboratoire de Résonance Magnétique Nucléaire, Institut Pasteur, CNRS URA 1129, Paris, France.
Prochnicka-Chalufour
A
A
Nieto
A R
AR
Torres
J A
JA
Nanard
N
N
Rodriguez
M H
MH
Possani
L D
LD
Delepierre
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000633:toxicity*; D023181:Antimicrobial Cationic Peptides; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000633:toxicity*; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development; D017433:Protein Structure, Secondary
D000962:Antimalarials; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C093645:Shiva 3