Choy SL, Bernin H, Aiba T, Bifeld E, Lender SC, Mühlenpfordt M, Noll J, Eick J, Marggraff C, Niss H, Roldán NG, Tanaka S, Kitamura M, Fukase K, Clos J, Tannich E, Fujimoto Y, Lotter H Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection Scientific Reports7(1) (2017)
9472
/Variants 0/-+
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Pam-(1-2)-L-myoIno-(1--P--3)--Gro
/Variants 0/ is:
Mon-(1-1)-
OR (exclusively)
?%LIP-(1-1)-
The structure was elucidated in this paper NCBI PubMed ID:28842620 Publication DOI:10.1038/s41598-017-09894-8 Journal NLM ID:101563288 Publisher: London: Nature Publishing Group Correspondence: lotterbnitm.de Institutions: Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, Department of Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan, Graduate School of Science, Osaka University, Toyonaka, Japan, Junior Group of Allergobiochemistry, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany
Intracellular pathogens belonging to the genus Leishmania have developed effective strategies that enable them to survive within host immune cells. Immunostimulatory compounds that counteract such immunological escape mechanisms represent promising treatment options for diseases. Here, we demonstrate that a lipopeptidephosphoglycan (LPPG) isolated from the membrane of a protozoan parasite, Entamoeba histolytica (Eh), shows considerable immunostimulatory effects targeted against Leishmania (L.) major, a representative species responsible for cutaneous leishmaniasis (CL). Treatment led to a marked reduction in the number of intracellular Leishmania parasites in vitro, and ameliorated CL in a mouse model. We next designed and synthesized analogs of the phosphatidylinositol anchors harbored by EhLPPG; two of these analogs reproduced the anti-leishmanial activity of the native compound by inducing production of pro-inflammatory cytokines. The use of such compounds, either alone or as a supportive option, might improve the currently unsatisfactory treatment of CL and other diseases caused by pathogen-manipulated immune responses.
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