Glycoproteins with homogeneous glycosylation to define unexplored lectin binding properties

Description du projet

Décoder la spécificité des lectines pour la glycobiologie du cancer

La glycosylation aberrante (la fixation de sucres aux protéines et aux lipide) est une caractéristique du cancer. Les lectines sont des protéines liant les glucides, présentes dans la plupart des organismes vivants, qui se sont révélées être des outils inestimables pour la recherche sur le cancer. Avec le soutien du programme Actions Marie Skłodowska-Curie, le projet GlycoScope entend faire la lumière sur la liaison des lectines à des modèles de glycosylation inexplorés dans le cancer. Il combinera des informations moléculaires à l’échelle atomique issues de la spectroscopie par résonance magnétique nucléaire avec des tests fonctionnels de lectines largement utilisés. Grâce à des méthodes chimioenzymatiques, GlycoScope synthétisera des glycoprotéines pures avec des modifications de sucres homogènes et naturelles, éliminant de la sorte l’hétérogénéité perturbatrice présente dans les systèmes naturels. Les résultats permettront de faire progresser le domaine de la glycobiologie du cancer.

Objectif

GlycoScope aims to provide key answers for the understanding of lectin binding to complex and previously unexplored glycosylation patterns related to cancer. Main aim is to integrate atomic-level insights into molecular recognition, obtained through Nuclear Magnetic Resonance (NMR) spectroscopy, with widely used lectin-based assays for glycosylation analysis. This combined strategy will enable a precise chemical definition of lectin specificities and refine one of the most commonly applied tools in glycosciences. To achieve this, and as a major challenge, pure glycoproteins presenting homogeneous glycoepitopes will be generated through chemoenzymatic synthesis, ensuring natural glycan presentation and providing the optimal platform for lectin-based assays, while overcoming the critical drawback of heterogeneity that characterizes natural glycosylation. Polylactosamine (PLN) modification through I-branching and terminal sialylation will be interrogated for their binding to PLN- binding lectins, including plant lectins commonly used to characterize glycosylation and galectins, immune lectins involved in health and disease.
Complementary, GlycoScope offers Dr. Soriano a unique opportunity to broaden his training beyond his current focus on natural products and synthetic chemistry. It will provide him with interdisciplinary expertise in Molecular Recognition, Biological Chemistry and Glycobiology, thereby greatly enhancing his future employability and broadening his scientific perspective. Alongside the acquisition of specific technical skills—including NMR-based molecular recognition, chemoenzymatic chemistry, and molecular biology and protein biochemistry—Dr. Soriano will also benefit from the outstanding scientific environment and advanced training opportunities available at CIC bioGUNE. At the same time, the host-group will highly benefit from Dr. Sorianos´ expertise in chemical synthesis and purification procedures, key for the development of the project.