STRUCTURAL STUDIES ON THE PLASMODIUM SURFACE PROTEINS

本文研究了疟原虫的结构和疟原虫的种类

In this study of the structure of Plasmodium malaria parasite species and stage-specific surface proteins we propose to prepare synthetic peptide segments of various parts of the polypeptide chain including the tandem repeats, a common feature of all malaria Plasmodium parasite surface proteins studied to date and study the conformation of the synthetic peptide corresponding to the immunodominant tandem repeats (epitopes) using NMR and circular dichroism. The surface properties of these synthetic epitopes and their synthetically prepared polymers will be measured in monolayer experiments. We shall also design peptide analogs of the tandemly repeated epitopes and other peptide segments in an attempt to raise high titer and high affinity antibodies which may be effective in developing a vaccine against these malaria parasites. The P. Knowlesi circumsporozoite protein will be expressed in yeast and E. coli and purified by high performance liquid chromatography and affinity chromatography using antibodies directed against the synthetic peptides as well as against sporozoite extracts. The primary and secondary structure of the expressed protein will be analyzed, the two possible disulfide bridges, if they exist, will be determined and its conformation will be analyzed by CD and NMR. Finally, an attempt will be made to develop malaria vaccine using synthetic peptides or their analogs corresponding to segments of the CS protein.