Liao Kuo-Shiang, Zhou Yixuan, Chung Cinya, Kung Chih-Chuan, Ren Chien-Tai, Wu Chung-Yi, Lou Yi-Wei, Chuang Po-Kai, Imre Balázs, Hsieh Yves S Y, Wong Chi-Huey
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Department of Chemistry, The Scripps Research Institute, San Diego, CA 92037, USA.
Molecules. 2025 May 22;30(11):2264. doi: 10.3390/molecules30112264.
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.
细胞表面的异常糖基化，尤其是唾液酸化，通常与癌症进展和免疫抑制有关。据报道，阶段特异性胚胎抗原-4（SSEA-4）过度唾液酸化生成二唾液酸Gb5（DSGb5）会触发Siglec-7识别并抑制自然杀伤细胞（NK）介导的靶细胞杀伤。在本研究中，探索了高效的化学酶法和可编程的一锅法来合成DSGb5和相关唾液酸苷，用于组装聚糖微阵列，并评估其与免疫检查点抑制相关的Siglec-7、9、10和15的结合特异性。结果表明，DSGb5与这些Siglec的结合较弱；然而，一种截短的糖基化聚糖被鉴定出与Siglec-10有强结合，解离常数为50 nM，并对Siglec-10与乳腺癌细胞的相互作用表现出显著抑制作用。
