Chemoenzymatic Synthesis of Globo-series Glycosphingolipids and Evaluation of Their Immunosuppressive Activities.

Glycosphingolipids (GSLs) play essential roles in many important biological processes, making them attractive synthetic targets. In this paper, a viable chemoenzymatic method is described for the synthesis of globo-series GSLs, namely, Gb4, Gb5, SSEA-4, and Globo H. The strategy uses a chemically synthesized lactoside acceptor equipped with a partial ceramide structure that is uniquely extended by glycosyltransferases in a highly efficient one-pot multiple enzyme (OPME) procedure. A direct and quantitative conversion of Gb4 sphingosine to Globo H sphingosine is achieved by performing two-sequential OPME glycosylations. A reduction and N-acylation protocol allows facile incorporation of various fatty acids into the lipid portions of the GSLs. The chemically well-defined lipid-modified Globo H-GSLs displayed some differences in their immunosuppressive activities, which may benefit the structural modifications of Globo H ceramides in finding new types of immunosuppressive agents. The strategy outlined in this work should be applicable to the rapid access to other complex GSLs. © 2022 Wiley-VCH GmbH.

Citation

Pei-Yun Chiang, Avijit K Adak, Wei-Lun Liang, Chen-Yen Tsai, Hsin-Kai Tseng, Jing-Yan Cheng, Jih Ru Hwu, Alice L Yu, Jung-Tung Hung, Chun-Cheng Lin. Chemoenzymatic Synthesis of Globo-series Glycosphingolipids and Evaluation of Their Immunosuppressive Activities. Chemistry, an Asian journal. 2022 Aug 15;17(16):e202200403

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PMID: 35616406

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