新的键偶联化学探索聚糖识别。

IF 10.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
ACS Central Science Pub Date : 2025-04-23 eCollection Date: 2025-05-28 DOI:10.1021/acscentsci.4c02124
Tianwei Jia, Akul Y Mehta, Catherine A Tilton, Ea Kristine Clarisse Tulin, Lauren E Pepi, Lukas Muerner, Stephan von Gunten, Jamie Heimburg-Molinaro, Sean R Stowell, Richard D Cummings
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引用次数: 0

摘要

蛋白质对聚糖的特异性识别在许多生物过程和免疫反应中都很重要。在这里,我们提出了一种用新型连接剂MTZ(3-(甲氧基氨基)-丙胺添加到生物正交功能四嗪标签上)衍生游离聚糖的一般方法,该方法利用点击化学产生多种聚糖偶联平台。这种衍生化保留了聚糖的完整性,是可逆的和可量化的,并结合了一个生物正交四嗪标签,用于点击耦合。通过生物素- peg11 - tco(反式环烯)间隔器,将ABO-(H)血型mtz -聚糖库有效地偶联到avidin Luminex珠上,产生一个多重阵列,该阵列可在高通量Luminex方法中使用多种凝集素和抗体进行重复性查询。我们还在多个连续稀释的人血清样本中快速分析了抗糖多糖IgG、IgM和IgA抗体,揭示了每种血清中抗糖多糖反应的独特谱。多糖以高密度(~ 19-24个聚糖/BSA)高效偶联到牛血清白蛋白(BSA)上,生成一个新的糖蛋白文库,该文库可用于微阵列格式,提供与Luminex方法等效的结果。新糖蛋白有许多用途,包括作为糖基转移酶的受体,正如我们在ST6Gal1唾液基转移酶的测定中所展示的那样。这些简单有效的技术极大地扩展了可用于探索甘聚糖- gbp相互作用的工具箱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel Click Coupling Chemistry to Explore Glycan Recognition.

Specific recognition of glycans by proteins is important in many biological processes and immune responses. Here we present a general approach for derivatizing free glycans with a novel linker MTZ (3-(methoxyamino)-propylamine added to a bioorthogonal-functional tetrazine tag) that exploits click chemistry to generate multiple platforms of glycan coupling. This derivatization preserves glycan integrity, is reversible and quantifiable, and incorporates a bioorthogonal tetrazine tag for click coupling. A library of ABO-(H) blood group MTZ-glycans was efficiently conjugated to avidin Luminex beads through a Biotin-PEG11-TCO (trans-cyclooctene) spacer, generating a multiplex array that was reproducibly interrogated in a high-throughput Luminex approach with multiple lectins and antibodies. We also rapidly profiled antiglycan IgG, IgM, and IgA antibodies in multiple, serially diluted human serum samples, revealing unique repertoires of antiglycan responses in each sera. Glycans were efficiently coupled to bovine serum albumin (BSA) at a high density (∼19-24 glycans/BSA) to generate a neoglycoprotein library that was useful in microarray formats that provided results equivalent to those obtained from the Luminex approach. Neoglycoproteins have many uses, including serving as acceptors for glycosyltransferases, as we demonstrate for assays of ST6Gal1 sialyltransferase. These facile and efficient technologies significantly expand the toolbox available to explore glycan-GBP interactions.

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来源期刊
ACS Central Science
ACS Central Science Chemical Engineering-General Chemical Engineering
CiteScore
25.50
自引率
0.50%
发文量
194
审稿时长
10 weeks
期刊介绍: ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.
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