Mechanistic Studies for the Rational Design of Multivalent Glycodendrimers |
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Authors: | Dr. Yoshiyuki Manabe Dr. Masato Tsutsui Kohtaro Hirao Risako Kobayashi Dr. Hiroshi Inaba Prof. Kazunori Matsuura Daisuke Yoshidome Kazuya Kabayama Prof. Koichi Fukase |
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Affiliation: | 1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan;2. Department of Chemistry and Biotechnology, Graduate School of Engineering, Center for Research on Green Sustainable Chemistry, Tottori University, 4-101 Koyama-Minami, Tottori, 680-8552 Japan;3. Schrödinger K.K., 17F Marunouchi Trust Tower North, 1-8-1 Marunouchi, Chiyoda-ku, Tokyo, 100-0005 Japan;4. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan Forefront Research Center, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043 Japan |
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Abstract: | We have synthesized B-antigen-displaying dendrimers (16-mers) with different sizes and evaluated their affinity to their IgM antibody in order to investigate which design features lead to effective multivalency. Unexpectedly, the smallest dendrimer, which cannot chelate the multiple binding sites of IgM, clearly exhibited multivalency, together with an affinity similar to or higher than those of the larger dendrimers. These results indicate that the statistical rebinding model, which involves the rapid exchange of clustered glycans, significantly contributes to the multivalency of glycodendrimers. Namely, in the design of glycodendrimers, high-density glycan presentation to enhance statistical rebinding should be considered in addition to the ability to chelate multiple binding sites. This notion stands in contrast to the currently prevailing scientific consensus, which prioritizes the chelation model. This study thus provides new and important guidelines for molecular design of glycodendrimers. |
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Keywords: | ABO blood type dendrimer glycan IgM antibody multivalency |
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