Synthesis of Leishmania´s LPG and GIPLs constituents for vaccine and diagnostic test development

CAROLINA TOULOUMDJIAN; ELEONORA ELHALEM; COMIN, MARÍA J.; LUCÍA, GANDOLFI DONADÍO

Buenos Aires

Congreso; DRUG DISCOVERY FOR NEGLECTED DISEASES INTERNATIONAL CONGRESS 2018Book of abstracts4t ? 6t December 2018Facultad de Farmacia y Bioquímica - Universidad de Buenos AiresCiudad Autónoma de Buenos Aires, ArgentinaResNet NPND4t Scientific Meeting of the Rese; 2018

Facultad de Farmacia y Bioquímica - Universidad de Buenos Aires Ciudad Autónoma de Buenos Aires, Argentina

Leishmaniasis is a group of diseases caused by the trypanosomatid Leishmania. In Argentina, american tegumentary leishmaniasis (LTA) is endemic. There is no human vaccine available, the existing treatments are expensive, have adverse effects and resistance cases have been reported. Hence, diagnostic test to differentiate acutely diseased from clinically asymptomatic patients and fully protective vaccines against the diseases are highly desired.1 Vaccine based on carbohydrate antigens are a viable option for parasitic vaccine development. Synthetic carbohydrate substructures of cell surface glycans have been a suitable tool to delineate the structure-function relationships as the basis of rational vaccine design. The identification of an epitope that will eventually induce protective immunity is the major challenge.2The LPG (lipophosphoglycan) and GIPLs (glycoinositol phospholipids) of Leishmania are interesting targets for this purpose because they are highly immunogenic and represents one of the most abundant surface glycans.2 An unusual feature of LPG and GIPLs is the galactofuranose (Galf), exclusively found in nonmammalian species.With the idea of identifying the minimum substructure unit of GIPLs and LPG capable of being recognized by the immune system3, we report the synthesis of the first group of galactofuranosides (1-2). The incorporation of the amino linker (L) will serve to immobilize the sugars in a suitable surface to analyze the antigenicity by screening against infected sera. The first step for the synthesis of 1 consisted in the glycosylation between 3 and 5 to give 6 with 92% yield. 1H NMR of the product confirmed the β configuration of the glycosidic linkage. Finally, basic treatment and subsequent hydrogenolysis gave 1 with 90% yield.To build the Galf-β-(1-3)-Manp linkage of 2, glycosidation of 3 with an excess of mannoside 4 was carried out. The regioselectivity of the reaction in favor of the β-(1-3) linkage was confirmed