Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition
Aberrant glycosylation, especially sialylation, on cell surface is often associated with cancer progression and immunosuppression. Over-sialylation of stage-specific embryonic antigen-4 (SSEA-4) to generate disialylGb5 (DSGb5) was reported to trigger Siglec-7 recognition and suppress NK-mediated tar...
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2025-05-01
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| author | Kuo-Shiang Liao Yixuan Zhou Cinya Chung Chih-Chuan Kung Chien-Tai Ren Chung-Yi Wu Yi-Wei Lou Po-Kai Chuang Balázs Imre Yves S. Y. Hsieh Chi-Huey Wong |
| author_facet | Kuo-Shiang Liao Yixuan Zhou Cinya Chung Chih-Chuan Kung Chien-Tai Ren Chung-Yi Wu Yi-Wei Lou Po-Kai Chuang Balázs Imre Yves S. Y. Hsieh Chi-Huey Wong |
| author_sort | Kuo-Shiang Liao |
| collection | DOAJ |
| description | Aberrant glycosylation, especially sialylation, on cell surface is often associated with cancer progression and immunosuppression. Over-sialylation of stage-specific embryonic antigen-4 (SSEA-4) to generate disialylGb5 (DSGb5) was reported to trigger Siglec-7 recognition and suppress NK-mediated target killing. In this study, efficient chemo-enzymatic and programmable one-pot methods were explored for the synthesis of DSGb5 and related sialosides for assembly of glycan microarrays and evaluation of binding specificity toward Siglecs-7, 9, 10, and 15 associated with immune checkpoint inhibition. The result showed weak binding of DSGb5 to these Siglecs; however, a truncated glycolyl glycan was identified to bind Siglec-10 strongly with a dissociation constant of 50 nM and exhibited a significant inhibition of Siglec-10 interacting with breast cancer cells. |
| format | Article |
| id | doaj-art-c40379fbf22c4ff4ba1d58e39d593d23 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-c40379fbf22c4ff4ba1d58e39d593d232025-08-20T02:33:02ZengMDPI AGMolecules1420-30492025-05-013011226410.3390/molecules30112264Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint InhibitionKuo-Shiang Liao0Yixuan Zhou1Cinya Chung2Chih-Chuan Kung3Chien-Tai Ren4Chung-Yi Wu5Yi-Wei Lou6Po-Kai Chuang7Balázs Imre8Yves S. Y. Hsieh9Chi-Huey Wong10Genomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanDepartment of Chemistry, The Scripps Research Institute, San Diego, CA 92037, USASchool of Pharmacy, Taipei Medical University, Taipei 110, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei 110, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanAberrant glycosylation, especially sialylation, on cell surface is often associated with cancer progression and immunosuppression. Over-sialylation of stage-specific embryonic antigen-4 (SSEA-4) to generate disialylGb5 (DSGb5) was reported to trigger Siglec-7 recognition and suppress NK-mediated target killing. In this study, efficient chemo-enzymatic and programmable one-pot methods were explored for the synthesis of DSGb5 and related sialosides for assembly of glycan microarrays and evaluation of binding specificity toward Siglecs-7, 9, 10, and 15 associated with immune checkpoint inhibition. The result showed weak binding of DSGb5 to these Siglecs; however, a truncated glycolyl glycan was identified to bind Siglec-10 strongly with a dissociation constant of 50 nM and exhibited a significant inhibition of Siglec-10 interacting with breast cancer cells.https://www.mdpi.com/1420-3049/30/11/2264sialyl SSEA-4programmablechemoenzymatic synthesisglycolyl sialic acidimmune checkpoint |
| spellingShingle | Kuo-Shiang Liao Yixuan Zhou Cinya Chung Chih-Chuan Kung Chien-Tai Ren Chung-Yi Wu Yi-Wei Lou Po-Kai Chuang Balázs Imre Yves S. Y. Hsieh Chi-Huey Wong Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition Molecules sialyl SSEA-4 programmable chemoenzymatic synthesis glycolyl sialic acid immune checkpoint |
| title | Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition |
| title_full | Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition |
| title_fullStr | Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition |
| title_full_unstemmed | Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition |
| title_short | Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition |
| title_sort | chemical and enzymatic synthesis of disialylgb5 and other sialosides for glycan array assembly and evaluation of siglec mediated immune checkpoint inhibition |
| topic | sialyl SSEA-4 programmable chemoenzymatic synthesis glycolyl sialic acid immune checkpoint |
| url | https://www.mdpi.com/1420-3049/30/11/2264 |
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