Synthesis of Discrete Glyco-oligomers mimicking GM1 glycans.

Glycans are compounds formed by the linkage of several monosaccharides and are abundant on the cell surface in living organisms. Depending on the type and structure of the monosaccharides forming the glycan, it is known that they can specifically recognize various proteins. Cholera is a representative orally transmitted infectious disease, with over 20,000 deaths and over 1.3 million infections reported annually. The Cholera toxin B subunit (CTB) recognizes and binds to GM1 (a type of ganglioside) present on the human cell surface, allowing the toxic unit to be taken into the intestines and initiate infection. While polysaccharides like GM1 possess various physiological activities, their extraction and purification from nature are costly. GM1 is composed of several monosaccharides, each of which can be considered a "glycan module," a unit of molecular recognition. Materials mimicking GM1 bind to CTB and act as cholera infection inhibitors. To date, our laboratory has reported the synthesis of GM1-mimicking glycan polymers using the glycan module method. However, structural heterogeneity, such as the sequence and molecular weight of the sugar side chains, poses challenges due to the uncertainty of the interaction strength and binding ratio. This study aims to synthesize discrete glycooligomers that mimic GM1 glycans. Polymers obtained by conventional controlled radical polymerization (such as ATRP and RAFT) inevitably have a molecular weight distribution (polydispersity) derived from statistical growth reactions. While it is possible to bring the degree of dispersion (Đ) close to 1.0, it is difficult to extract only molecules with a completely single degree of polymerization. Therefore, we aim to overcome the variability in the binding mode with CTB by applying the discrete oligomer synthesis strategy first reported by Hawker et al. to glycan polymers and synthesizing GM1-mimicking compounds with completely defined molecular weight and sequence.