Synthesis, screening and use of parasitic O-glycans and mimetics for improved C-type lectin receptor targeting
- Autores: Julie Thanh Pham
- Directores de la Tesis: Niels-Christian Reichardt (dir. tes.), Claudio Palomo Nicolau (dir. tes.), Jesús Jiménez Barbero (dir. tes.)
- Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2018
- Idioma: inglés
- Tribunal Calificador de la Tesis: Alma Rosa López Álvarez (presid.), Francisco Corzana López (secret.), Marcelo Eduardo Guerin (voc.)
- Programa de doctorado: Programa de Doctorado en Química Sintética e Industrial por la Universidad del País Vasco/Euskal Herriko Unibertsitatea y la Universidad Pública de Navarra
- Materias:
- Enlaces
- Tesis en acceso abierto en: ADDI
- Resumen
O-glycans from the helminth Schistosoma mansoni represent promising leads in the development of immunomodulatory compounds via the interaction with C-type lectin receptors (CLRs), as reported for DC-SIGN, L-SIGN, Langerin and MGL. We undertook the chemoenzymatic synthesis of an O-glycan library inspired from structures previously isolated from the helminth. We described the synthesis of parasitic O-glycan cores mucin core 2 and the S.mansoni specific core. Enzymatic elongations towards a library of O-glycans were limited to the Galß-1,6GalNAc arm of the cores owing to an unanticipated acceptor specificity of the recombinant glycosyltransferase LgtA_X. Synthesized as aminopentyl glycosides, eight O-glycans were obtained and were printed on-chip alongside N-glycans available from our laboratory. The array was enzymatically modified using a FucT from H.pylori in conjunction with either a fucose or 6-azido-fucose donor and arrayed against a selection of CLRs, revealing interesting features in the CLR specificity and suggesting the existence of exploitable chemical space for CLR targeting.
