Carbohydrates as potentially versatile core subcarriers for multivalent immunogens

Abstract

Synthetic multivalent glycoclusters that carry carbohydrate antigen epitopes have been recognized as promising candidates for the development of carbohydrate based vaccines. Here we describe a convergent strategy for the synthesis of conjugation-ready multivalent glycoclusters using sugars as versatile core subcarriers. d-Glucose and gentiobiose were converted into poly-alkyne functionalized cores which were then decorated with an azide bearing model ligand d-glucose using click chemistry, to form structurally well-defined tetra- and heptavalent glycoclusters. Each cluster was conjugated to a model protein bovine serum albumin (BSA) by squaric acid chemistry. Carbohydrate clusters can be prepared in a variety of sizes and spatial arrangements by altering the structure and configuration of the core, depending on the mono-, or oligosaccharides used for their assembly. It is suggested that the use of carbohydrate as core subcarriers provides an opportunity to tailor the size and topology of antigens and modify multivalent presentation of immunogens in a way to optimize cluster effect for stronger immunoreactivity.

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Kovac and co-workers utilized d -glucose and gentiobiose as model sugars and 6-azido-hexyl-2,3,4,6-tetra- O -acetyl-β- d -glucopyranoside as a model hapten to give high yields of the polyalkyne functionalized cores. The authors successfully produced well-organized tetravalent- and heptavalent glycoclusters ( 985 and 986 ) (Figure ) as suitable subcarriers for multivalent immunogens via a modular CuAAC click cycloaddition protocol . The designed conjugates are structurally single-ended conjugation models and utilized as well-defined building blocks for the vaccines along with the non-cross-linked molecular arrangement.…”