GLYCOBIOLOGY OF THE MALARIA PARASITE TMP PILOT NIAID

本提案的总体目标是完成结构性 分析恶性疟原虫蛋白的GPI锚，鉴定 不寻常的取代基，涉及特定的结构特征， 免疫原性和疾病病理学方面，并确定影响 GPI合成的抑制作用。 我们已经证明GPI锚合成是主要的碳水化合物- 相关的蛋白质修饰进行的寄生虫，N- 连接的糖基化的频率非常低， 糖基化要么完全不存在，要么处于极低水平。 此外，GPI合成的抑制强烈地抑制了细胞的生长。 寄生虫，这表明抗疟疾药物开发的目标。

The overall goals of this proposal are to complete the structural analysis of the GPI anchors of the proteins of P. falciparum, identify unusual substituents, relate specific structural features to immunogenecity and aspects of disease pathology and to define effects of the inhibition of GPI synthesis on the parasite. We have shown that GPI anchor synthesis is the major carbohydrate- related protein modification carried out by the parasite and, that N- linked glycosylation is of very low frequency and that O-linked glycosylation is either completely absent or at extremely low levels. In addition, inhibition of GPI synthesis is strongly inhibitory to the parasite suggesting a target for anti-malarial drug development.