New glycosylated materials for lectin inhibition, detection and targeting

Abstract

The growing knowledge of the biological role played by the glycoside cluster effect and the growing interest in new biocompatible nanomaterials prompted us to synthesize new glycosylated compounds and assemble new glycosylated materials able to recognize specific lectins with inhibition, detection and targeting purposes. These recognition processes, that take place through carbohydrate-protein interactions and are characterized by high selectivity and efficiency, combine a multivalent presentation of carbohydrates and the characteristic of the materials, such as monolayers on gold nanopaticles (AuNPs) and surfaces or the self-assembly properties of particular luminescent complexes. Calixarenes were chosen as privileged scaffolds to functionalize such materials because they offer the unique opportunity to easily tune the valency, the shape and structure of the multivalent carbohydrate presentation. In this Ph.D. thesis concerns we describe a binding study of some new galactosyl- and lactosylcalix[4]arene, in different structures, toward Gal-3, using SPR studies. These compounds showed different affinity for Gal-3 with a selectivity which depends on the type of sugar presented and on their disposition around the macrocyclic structure, pointing out the importance of the multivalent presentation in space of the glycosyl units. Moreover, a new non covalent functionalization of AuNPs with glycocalix[4]arene was carried out, and allow a fast and convenient strategy to obtain new water soluble AuNPs functionalized with glycocalixarene scaffolds and therefore exposing a carbohydrate coating on the surface of the NP similar to that present on the surface of cells and called glycocalyx. Finally, the synthesis and characterization of luminescent Platinum (II) complexes functionalized with sugars on the ancillary ligand in order to make these complexes, usually liphophilic and soluble only in organic solvents, water soluble and to study their facilitated uptake by the cells, is described. These compounds could potentially enter and selectively stain cells or particular compartments inside cell (such as cytoplasm, organelles or the nucleus) thanks to the interaction of the sugar units with lectins or other carbohydrate binding proteins.