Published papers

We propose a de novo glycan display that combines metabolic labeling and a glycan-caging strategy as a facile editing method for cell-surface glycans. This method enables the introduction of antigen glycans onto cancer cells to induce immune responses through antibody recruiting. The caging strategy prevents the capture of α-rhamnose (an antigen glycan) by their endogenous antibodies during the introduction of the glycan to the targeted cell surface, and subsequent uncaging successfully induces immune responses. Therefore, this study proposes a practical method for editing the cell-surface glycocalyx under promiscuous conditions, such as those in vivo, which paves the way for the development of glycan function analysis and regulation.

Abstract We have established an innovative protective approach that disrupts intermolecular interactions to enhance substrate reactivity. Specifically, diacetylimide protection of acetamide prevents the formation of hydrogen bonds, while the incorporation of tert-butyl groups on the aromatic protecting group disrupts π-stacking interactions, both of which culminate in heightened reactivity in glycosylations. We explored the synergistic implementation of these protective measures and applied them to the synthesis of 6-sulfo sialyl Lewis X.

Droplet levitation in air represents a promising containerless, plastic-free reaction vessel for chemical biology. In this study, we show that dimethyl sulfoxide (DMSO), a hygroscopic solvent that absorbs moisture from air, is a suitable additive for long-term levitation and for copper-catalyzed alkyne–azide cycloaddition reactions in levitated droplets. When the volume of solvent mixtures composed of water and water-miscible organic solvents was precisely monitored, the evaporation of DMSO-containing aqueous mixtures was negligible, and their volume increased under high humidity. Furthermore, the click reaction in a DMSO–water mixture under levitation proceeded faster and with higher yield than the same reaction performed in a shaken tube. Together, these results suggest that ultrasonic levitation has the potential not only to alter conventional experimental workflows in chemical biology, but also to enable capture of moisture from ambient air.

In this study, we synthesized disaccharide oxazolines 3 and 4 bearing a tetrazine moiety. These compounds are recognized as substrates by Endo-S2 and efficiently undergo one-pot glycan remodeling reactions. Furthermore, combining two orthogonal click chemistry achieved, site-specific dual functionalization into a single antibody.

Individual interactions between glycans and their receptors are usually weak, although these weak interactions can combine to realize a strong interaction (multivalency). Such multivalency plays a crucial role in the recognition of host cells by pathogens. Glycodendrimers are useful materials for the reconstruction of this multivalent interaction. However, the introduction of a large number of glycans to a dendrimer core is fraught with difficulties. We herein synthesized antipathogenic glycodendrimers using the self-activating click chemistry (SACC) method developed by our group. The excellent reactivity of SACC enabled the efficient preparation of sialyl glycan and Gb3 glycan dendrimers, which exhibited strong avidity toward hemagglutinin on influenza virus and Shiga toxin B subunit produced by Escherichia coli, respectively. We demonstrated the usefulness of SACC-based glycodendrimers as antipathogenic compounds.