Chemoenzymatic Tagging of Tn/TF/STF Antigens in Living Systems

IF 2.3 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY

Israel Journal of Chemistry Pub Date : 2023-09-15 DOI:10.1002/ijch.202300081

Yi Yang, Mingkuan Chen, Mengyao Wu, Senlian Hong, Bing Gao, Yonghui Liu, Chenhua Yu, Travis S. Young, Digantkumar Gopaldas Chapla, Jeong-Yeh Yang, John R. Cappiello, Jie P. Li, K. Barry Sharpless, Kelley W. Moremen, Peng Wu

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引用次数: 0

Abstract

Truncated mucin-type O-glycans, such as Tn-associated antigens, are aberrantly expressed biomarkers of cancer, but remain challenging to target. Reactive antibodies to these antigens either lack high affinity or are prone to antigen escape. Here, we have developed a robust chemoenzymatic strategy for the global labeling of Tn-associated antigens, i. e. Tn (GalNAcα-O-Ser/Thr), Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, TF) and STF (Neu5Acα2-3Galβ1-3GalNAcα-O-Ser/Thr, STF) antigens, in human whole blood with high efficiency and selectivity. This method relies on the use of the O-glycan sialyltransferase ST6GalNAc1 to transfer a sialic acid-functionalized adaptor to the GalNAc residue of these antigens. By tagging, the adaptor functionalized antigens can be easily targeted by customized strategies such as, but not limited to, chimeric antigen receptor T-Cells (CAR-T). We expect this tagging system to find broad applications in cancer diagnostics and targeting in combination with established strategies.

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生物系统中Tn/TF/STF抗原的化学酶标记

截短的粘蛋白型O -聚糖，如Tn -相关抗原，是异常表达的癌症生物标志物，但仍然具有挑战性。这些抗原的反应性抗体要么缺乏高亲和力，要么易于抗原逃逸。在这里，我们开发了一种强大的化学酶策略，用于全球标记Tn相关抗原，即Tn (GalNAcα‐O‐Ser/Thr)， Thomsen‐Friedenreich (Galβ1‐3galnaa α‐O‐Ser/Thr, TF)和STF (Neu5Acα2‐3galnaβ 1‐3galnaa α‐O‐Ser/Thr, STF)抗原，具有高效率和选择性。该方法依赖于使用O -聚糖唾液基转移酶ST6GalNAc1将唾液酸功能化的适配器转移到这些抗原的GalNAc残基上。通过标记，适配器功能化抗原可以很容易地通过定制策略靶向，例如但不限于嵌合抗原受体T细胞(CAR - T)。我们期望这种标记系统在癌症诊断和靶向治疗中找到广泛的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Israel Journal of Chemistry 化学-化学综合

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The fledgling State of Israel began to publish its scientific activity in 1951 under the general heading of Bulletin of the Research Council of Israel, which quickly split into sections to accommodate various fields in the growing academic community. In 1963, the Bulletin ceased publication and independent journals were born, with Section A becoming the new Israel Journal of Chemistry. The Israel Journal of Chemistry is the official journal of the Israel Chemical Society. Effective from Volume 50 (2010) it is published by Wiley-VCH. The Israel Journal of Chemistry is an international and peer-reviewed publication forum for Special Issues on timely research topics in all fields of chemistry: from biochemistry through organic and inorganic chemistry to polymer, physical and theoretical chemistry, including all interdisciplinary topics. Each topical issue is edited by one or several Guest Editors and primarily contains invited Review articles. Communications and Full Papers may be published occasionally, if they fit with the quality standards of the journal. The publication language is English and the journal is published twelve times a year.