Synthesis and functional evaluation of glycodendrimers as high-affinity ligands by mimicking the multivalent interaction

概要

Multivalent interaction plays a crucial role on biological system. Influenza virus recognizes sialyl glycan on host cell by hemagglutinin (HA). This interaction is also enhanced by multivalent effect. Here, the author developed multivalent molecules targeting influenza virus. The author used glycodendrimers because they can display a large number of glycans in homogeneous manner.

The author achieved efficient synthesis of sialyl trisaccharide using one-pot synthesis. Sialyl trisaccharide and sialyl pentasaccharide were used for preparation of glycodendrimer. Self-activating Cu catalized click chemistry was applied for conjugation of glycan with poly lysine dendrimer core to give desired compounds in excellent yield (>90%). 8-mer and 16-mer glycodendrimers showed high affinity to HA (KD = 0.13-3.03 μM). Synthesis of antibody-recruiting molecules (ARM) using multivalency was investigated. ARM consist of TBT (target-binding terminus) and ABT (antibody-binding terminus). Although conjugation between sialyl glycodendrimer (TBT) and α-gal dendrimer (ABT) did not proceeded, the author achieved the synthesis of ARM using HSA as scaffold. Multivalent material using HSA as scaffold have been reported to show high affinity. Thus, synthesized HSA conjugate is expected to function as an effective ARM.