Chemo-Click：受体控制和生物正交的趋化因子连接，用于对耐药白血病 B 细胞进行实时成像

IF 14.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2024-10-23 DOI:10.1021/jacs.4c12035

Marco Bertolini, Lorena Mendive-Tapia, Utsa Karmakar, Marc Vendrell

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引用次数: 0

摘要

B 细胞白血病的耐药性以 CXCR5 和 CXCR3 趋化因子受体的共表达为特征，使其成为对患者进行分层的重要生物标志物。在此，我们首次报道了一种新型的可激活趋化因子平台，用于对耐药白血病 B 细胞进行选择性成像。将人类趋化因子 CXCL13 和 CXCL10 的 C 端衍生为生物正交的四嗪-BODIPY 和 BCN 基团后，它们仍能通过同源的 CXCR5 和 CXCR3 受体结合并内化，从而通过细胞内趋化因子连接，快速荧光标记 CXCR5+ CXCR3+ 耐药 B 细胞（而非药物敏感性白血病细胞）。这种模块化化学方法为具有不同趋化因子特征的细胞群的实时免疫分型提供了一种多用途策略，并将加速设计新的精准医疗工具，以推进血液肿瘤的个性化治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Chemo-Click: Receptor-Controlled and Bioorthogonal Chemokine Ligation for Real-Time Imaging of Drug-Resistant Leukemic B Cells

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Chemo-Click: Receptor-Controlled and Bioorthogonal Chemokine Ligation for Real-Time Imaging of Drug-Resistant Leukemic B Cells

Drug resistance in B cell leukemia is characterized by the coexpression of CXCR5 and CXCR3 chemokine receptors, making it a valuable biomarker for patient stratification. Herein, we report a novel platform of activatable chemokines to selectively image drug-resistant leukemic B cells for the first time. The C-terminal derivatization of the human chemokines CXCL13 and CXCL10 with bioorthogonal tetrazine-BODIPY and BCN groups retained binding and internalization via their cognate CXCR5 and CXCR3 receptors and enabled rapid fluorescence labeling of CXCR5+ CXCR3+ resistant B cells─but not drug-susceptible leukemic cells─via intracellular chemokine ligation. This modular chemical approach offers a versatile strategy for real-time immunophenotyping of cell populations with distinct chemokine profiles and will accelerate the design of new precision medicine tools to advance personalized therapies in blood tumors.

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来源期刊

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.