Design and Creativity in Synthesis of Multivalent Neoglycoconjugates

Abstract

From the authors' opinion, this chapter constitutes a modest extension of the seminal and inspiring contribution of Stowell and Lee on neoglycoconjugates published in this series [C. P. Stowell and Y. C. Lee, Adv. Carbohydr. Chem. Biochem., 37 (1980) 225-281]. The outstanding progresses achieved since then in the field of the "glycoside cluster effect" has witnessed considerable creativity in the design and synthetic strategies toward a vast array of novel carbohydrate structures and reflects the dynamic activity in the field even since the recent chapter by the Nicotra group in this series [F. Nicotra, L. Cipolla, F. Peri, B. La Ferla, and C. Radaelli, Adv. Carbohydr. Chem. Biochem., 61 (2007) 353-398]. Beyond the more classical neoglycoproteins and glycopolymers (not covered in this work) a wide range of unprecedented and often artistically beautiful multivalent and monodisperse nanostructures, termed glycodendrimers for the first time in 1993, has been created. This chapter briefly surveys the concept of multivalency involved in carbohydrate-protein interactions. The topic is also discussed in regard to recent steps undertaken in glycobiology toward identification of lead candidates using microarrays and modern analytical tools. A systematic description of glycocluster and glycodendrimer synthesis follows, starting from the simplest architectures and ending in the most complex ones. Presentation of multivalent glycostructures of intermediate size and comprising, calix[n]arene, porphyrin, cyclodextrin, peptide, and carbohydrate scaffolds, has also been intercalated to better appreciate the growing synthetic complexity involved. A subsection describing novel all-carbon-based glycoconjugates such as fullerenes and carbon nanotubes is inserted, followed by a promising strategy involving dendrons self-assembling around metal chelates. The chapter then ends with those glycodendrimers that have been prepared using commercially available dendrimers possessing varied functionalities, or systematically synthesized using either divergent or convergent strategies.

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

“…Thus, glyco-clusters showing the carbohydrate units directly connected to the core, glyco-dendrimers connected through a dendritic structure and glyco-polymers involving a polymeric backbone have intensively been investigated in recent years. 5,6,7,8,9 Fullerenes also have been employed as a biocompatible scaffold for the multivalent presentation of ligands, given the possibility of multiple functionalization on their convex surface. In particular, hexakis-adducts of [60]fullerene with a Th-symmetrical octahedral addition pattern have a unique three-dimensional structure which allows the introduction of six one-type or mixed-types addends.…”

Glycodendrimers: versatile tools for nanotechnology

“…The key to successful vaccines resulted from the fact that the common protein carriers contained at least one ~15-amino acids sequence (T cell epitopes) known to bind strongly to Major Histocompatibility Complex (MHC). Because B-cells possess surface immunoglobulins (Igs) that bind to multivalent carbohydrate antigens such as polymers and polysaccharides, it was anticipated that glycodendrimers (Chabre, Roy, 2009;Chabre, Roy, 2010) could also bind to these Igs and trigger signaling events leading to the production of low affinity and low specificity IgM antibodies. Moreover, some APCs express mannopyranoside binding receptors (lectins) known as DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 (Cluster of Differentiation 209) (Figdor, Van Kooyk, Adema, 2002).…”

Multimeric xanthates as carbonic anhydrase inhibitors

“…Especially, carbohydrate-protein interactions are notably weak at the monomer level, but can be tremendously enhanced if the ligand is displayed in a multivalent way 13 . Scientists have extensively studied the biophysical interactions among natural systems and created a plethora of artificial multivalent systems in order to understand the underlying mechanisms of multivalency [14][15][16][17][18][19][20][21][22] . The most scrutinized systems are likely lectin-carbohydrate dyads.…”