Investigation of strategies with potential for producing a phosphorylcholine-free version of the filarial nematode immunomodulator, ES-62.
Phosphorylcholine (PC) is found attached to N-type glycans of proteins secreted by filarial nematodes, where it appears to act as an immunomodulator. Based on information on the structure and biosynthesis of the PC-glycan of a major secreted protein, ES-62, strategies were designed with potential for preparing PC-free material to better understand the importance of PC in filarial nematode immunomodulation. The strategies involve either enzymatic removal of PC or inhibition of its attachment during ES-62 synthesis. No method tested was found to be 100% effective although approximately 70% removal was obtained by culturing worms in Et18OCH3. Reasons for failure to obtain complete absence of PC moieties are discussed in relation to the structure and synthesis of PC-glycans and in addition PC-glycan biosynthesis is briefly commented on as a target for chemotherapy.
Houston
K M
KM
Department of Immunology, University of Strathclyde, Glasgow, G4 0NR, UK.
Egan
C A
CA
García
P
P
Harnett
W
W
D000818:Animals; D004791:Enzyme Inhibitors / Q000378:metabolism; D004950:Esterases / Q000378:metabolism; D005368:Filariasis / Q000276:immunology / Q000378:metabolism; D005370:Filarioidea / Q000276:immunology* / Q000378:metabolism; D015801:Helminth Proteins / Q000096:biosynthesis / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010767:Phosphorylcholine / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
C435884:ES-62 protein, Acanthocheilonema viteae; D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D007155:Immunologic Factors; D010767:Phosphorylcholine; D004950:Esterases; D010727:Phosphoric Diester Hydrolases; D001619:beta-N-Acetylhexosaminidases