PREVENTION OF ATTACHMENT OF PHOSPHORYLCHOLINE TO A MAJOR EXCRETORY-SECRETORY PRODUCT OF ACANTHOCHEILONEMA-VITEAE USING TUNICAMYCIN

ES-62, a major excretory-secretory (ES) product of Acanthocheilonema v iteae, consists of a protein backbone with N-linked carbohydrate and t he immunomodulatory group phosphorylcholine (PC); it can, therefore, b e biosynthetically labeled with radioactive leucine, glucosamine, or c holine. Incubation of worms with tunicamycin results in an ES product whose secretion is partially blocked, which demonstrates reduced molec ular weight when employing leucine as radiolabel, and which lacks radi oactivity when employing glucosamine or choline as label. Furthermore, the retained ES product can be detected in somatic extracts of parasi tes exposed to tunicamycin, by its reactivity for antibodies against t he whole parasite product but not by antibodies against PC alone. Thes e results support the idea that PC is attached to ES-62 via an N-linke d glycan and hence are consistent with the recent observation that PC can be removed from ES-62 by the sugar-cleaving enzyme, N-glycosidase F. The implications of this structural information with respect to des igning inhibitors of PC attachment for use as chemotherapeutic agents, and also the advantage of such material in raising antibodies to fila rial ES, are discussed.