Multivalency in heterogeneous glycoenvironments: hetero-glycoclusters, -glycopolymers and -glycoassemblies

Abstract

Despite efficiently imitating functional ligand presentations in terms of valency and density, most of the reported multivalent carbohydrate prototypes barely reflect the inherent heterogeneity of biological systems, therefore underestimating the potential contribution of synergistic or antagonistic effects to molecular recognition events. To address this question, the design of novel molecular and supramolecular entities displaying different saccharide motifs in a controlled manner is of critical importance. In this review we highlight the current efforts made to synthesize heteromultivalent glycosystems on different platforms (peptides, dendrimers, polymers, oligonucleotides, calixarenes, cyclodextrins, microarrays, vesicles) and to evaluate the influence of heterogeneity in carbohydrateprotein (lectin, antibody) recognition phenomena. Although the number of publications on this topic is limited as compared to the huge volume of reports on homomultivalent sugar displays, the current body of results has already unravelled the existence of new binding mechanisms that operate in heterogeneous environments whose exact biological significance remains to be unveiled.

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers

“…A subsequent amide coupling by an additional GlcNS(6S) unit bearing a terminal amine linker would then form diantennary monomer 6 (Figure 2), which increases the local saccharide density to better mimic the heterogeneity of HS chains. 4,73 Furthermore, we hypothesize that placement of a secondary sugar moiety in such close proximity enhances the probability of statistical rebinding and can also force a secondary unit into other binding sites, thus, allowing 6 to bind to both heparin binding domains (HBD-1 and HBD-2). 20,23,6770 Additionally, the diantennary unit potentially mimics the trisaccharide that binds into the −1/−2/+1 subsites of heparanase, but removes the scissile bond, thereby preventing cleavage by bridging over the catalytic residues.…”

Regioselective Silyl/Acetate Exchange of Disaccharides Yields Advanced Glycosyl Donor and Acceptor Precursors

“…51, 52 Structurally defined multivalent lactose-containing clusters have also been designed for optimal galectin binding. 48, 53 As such, there is a need for ready access to differentially protected lactosides to further investigate these biological processes.…”

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

“…Generally, individual sugar units exhibit weak binding affinities to complementary proteins, while systems that incorporate several carbohydrate units, attached to an appropriate scaffold or self-assembled in nanoparticles, lead to higher binding affinities owing to the sum of the individual interactions [5]. The synthesis of sugar-decorated molecular systems represents a significant tool in glycobiology and glycomic research fields [6].…”