Synthesis, screening and use of parasitic O-glycans and mimetics for improved C-type lectin receptor targeting

  1. PHAM, JULIE THANH
Dirigida por:
  1. Niels-Christian Reichardt Director/a
  2. Claudio Palomo Nicolau Director/a
  3. Jesús Jiménez Barbero Director/a

Universidad de defensa: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Fecha de defensa: 21 de noviembre de 2018

Tribunal:
  1. Alma Rosa López Álvarez Presidente/a
  2. Francisco Corzana López Secretario/a
  3. Marcelo Eduardo Guerin Vocal
Departamento:
  1. Química Orgánica I

Tipo: Tesis

Teseo: 148488 DIALNET lock_openADDI editor

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.