Ligand-Controlled Stereoselective Synthesis and Biological Activity of 2-Exomethylene Pseudo-glycoconjugates: Discovery of Mincle-Selective Ligands.

Autor: Ikazaki T; Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, 812-8582, Japan., Ishikawa E; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka, 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Yamadaoka, Suita, Osaka, 565-0871, Japan., Tamashima H; Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, 812-8582, Japan., Akiyama H; Juntendo Advanced Research Institute for Health Science, Juntendo University, Tokyo, 113-8421, Japan.; RIKEN Center for Brain Science, Wako, Saitama, 351-0198, Japan., Kimuro Y; Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, 812-8582, Japan., Yoritate M; Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, 812-8582, Japan., Matoba H; Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, 812-8582, Japan., Imamura A; Department of Applied Bioorganic Chemistry and Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan., Ishida H; Department of Applied Bioorganic Chemistry and Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan., Yamasaki S; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka, 565-0871, Japan.; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Yamadaoka, Suita, Osaka, 565-0871, Japan., Hirai G; Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 May 22; Vol. 62 (22), pp. e202302569. Date of Electronic Publication: 2023 Apr 25.
DOI: 10.1002/anie.202302569
Abstrakt: Glycoconjugate analogues in which the sp 3 -hybridized C2 position of the carbohydrate structure (normally bearing a hydroxy group) is converted into a compact sp 2 -hybridized exomethylene group are expected to have unique biological activities. We established ligand-controlled Tsuji-Trost-type glycosylation methodology to directly prepare a variety of these 2-exomethylene pseudo-glycoconjugates, including glucosylceramide analogues, in an α- or β-selective manner. Glucocerebrosidase GBA1 cleaves these synthetic pseudo-β-glucosylceramides similarly to native glucosylceramides. The pseudo-glucosylceramides exhibit selective ligand activity towards macrophage-inducible C-type lectin (Mincle), but unlike native glucosylceramides, are inactive towards CD1d.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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