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Synthesis and biological activity of ganglioside GM3 analogues with a (S)-CHF-Sialoside linkage and an alkyne tag

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Abstract

The alkyne tag, consisting of only two carbons, is widely used as a bioorthogonal functional group due to its compactness and nonpolar structure, and various probes consisting of lipids bearing an alkyne tag have been developed. Here, we designed and synthesized analogues of ganglioside GM3 bearing an alkyne tag in the fatty acid moiety and evaluated the effect of the alkyne tag on the biological activity. To eliminate the influence of other factors such as degradation of the glycan chain when evaluating biological activity in a cellular environment, we introduced the tag into sialidase-resistant (S)-CHF-linked GM3 analogues developed by our group. The designed analogues were efficiently synthesized by tuning the protecting group of the glucosylsphingosine acceptor. The growth-promoting effect of these analogues on Had-1 cells was dramatically altered depending upon the position of the alkyne tag.

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The data underlying this study are available in the published article and its supplementary information files.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Prof. Shigeru Nishiyama and Prof. Kazunobu Toshima (Keio University) for their kind support. We are also grateful for Prof. Yukishige Ito (RIKEN, Osaka University) for a generous gift of sialic acid.

Funding

This study was partially supported by PRIME, BINDS, and SCARDA from the Japan Agency for Medical Research and Development, AMED, the JSPS KAKENHI (grants No. 22K14683, 21K19053, and 21H02070), Asian Chemical Biology Initiative, Naito Foundation, Terumo Life Science Foundation, Leap Foundation, and RIKEN project funding.

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Authors and Affiliations

  1. Synthetic Organic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1, Hirosawa, Wako, Saitama, 351-0198, Japan

    Eisuke Ota, Kana Oonuma, Marie Kato, Mikiko Sodeoka & Go Hirai

  2. RIKEN Center for Sustainable Resource Science, 2-1, Hirosawa, Wako, Saitama, 351-0198, Japan

    Kana Oonuma, Mikiko Sodeoka & Go Hirai

  3. Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Daiki Takeda, Hiroaki Matoba, Makoto Yoritate & Go Hirai

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  1. Eisuke Ota
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  2. Daiki Takeda
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  3. Kana Oonuma
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Contributions

G.H. and M.S. conceived this research and designed the experiments; E.O., D.T., M.K., H.M., and M.Y. performed the synthetic studies; K.O. performed the cell experiments; E.O., D.T., M.K., H.M., M.Y., and G.H, analyzed the data and wrote Supporting Information; G.H. and M.S. wrote the original draft of the manuscript; all authors contributed to its reviewing and editing.

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Correspondence to Mikiko Sodeoka or Go Hirai.

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Ota, E., Takeda, D., Oonuma, K. et al. Synthesis and biological activity of ganglioside GM3 analogues with a (S)-CHF-Sialoside linkage and an alkyne tag. Glycoconj J 40, 333–341 (2023). https://doi.org/10.1007/s10719-023-10111-0

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