Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition

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

doi:10.3390/molecules30112264

Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition

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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	2264
Journal	Molecules
Volume	30
Issue number	11
DOIs	https://doi.org/10.3390/molecules30112264
Publication status	Published - Jun 2025

Keywords

chemoenzymatic synthesis
glycolyl sialic acid
immune checkpoint
programmable
sialyl SSEA-4

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules30112264

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Liao, K. S., Zhou, Y., Chung, C., Kung, C. C., Ren, C. T., Wu, C. Y., Lou, Y. W., Chuang, P. K., Imre, B., Hsieh, Y. S. Y., & Wong, C. H. (2025). Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition. Molecules, 30(11), Article 2264. https://doi.org/10.3390/molecules30112264

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abstract = "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.",

keywords = "chemoenzymatic synthesis, glycolyl sialic acid, immune checkpoint, programmable, sialyl SSEA-4",

author = "Liao, {Kuo Shiang} and Yixuan Zhou and Cinya Chung and Kung, {Chih Chuan} and Ren, {Chien Tai} and Wu, {Chung Yi} and Lou, {Yi Wei} and Chuang, {Po Kai} and Bal{\'a}zs Imre and Hsieh, {Yves S.Y.} and Wong, {Chi Huey}",

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year = "2025",

month = jun,

doi = "10.3390/molecules30112264",

language = "English",

volume = "30",

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AU - Liao, Kuo Shiang

AU - Zhou, Yixuan

AU - Chung, Cinya

AU - Kung, Chih Chuan

AU - Ren, Chien Tai

AU - Wu, Chung Yi

AU - Lou, Yi Wei

AU - Chuang, Po Kai

AU - Imre, Balázs

AU - Hsieh, Yves S.Y.

AU - Wong, Chi Huey

PY - 2025/6

Y1 - 2025/6

N2 - 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.

AB - 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.

KW - chemoenzymatic synthesis

KW - glycolyl sialic acid

KW - immune checkpoint

KW - programmable

KW - sialyl SSEA-4

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Chemical and Enzymatic Synthesis of DisialylGb5 and Other Sialosides for Glycan Array Assembly and Evaluation of Siglec-Mediated Immune Checkpoint Inhibition

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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