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化疗点击:受体控制和生物正交趋化因子连接用于耐药性白血病 B 细胞的实时成像。

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

机构信息

Centre for Inflammation Research, The University of Edinburgh, Edinburgh EH16 4UU, U.K.

IRR Chemistry Hub, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, U.K.

出版信息

J Am Chem Soc. 2024 Nov 6;146(44):30565-30572. doi: 10.1021/jacs.4c12035. Epub 2024 Oct 23.

DOI:10.1021/jacs.4c12035
PMID:39441736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11544607/
Abstract

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.

摘要

B 细胞白血病的耐药性表现为 CXCR5 和 CXCR3 趋化因子受体的共表达,使其成为患者分层的有价值的生物标志物。在此,我们首次报道了一种新型的趋化因子激活平台,可选择性地对耐药性白血病 B 细胞进行成像。通过生物正交四嗪-BODIPY 和 BCN 基团对人趋化因子 CXCL13 和 CXCL10 的 C 末端进行衍生化,保留了与它们同源的 CXCR5 和 CXCR3 受体的结合和内化,并通过细胞内趋化因子连接快速标记 CXCR5+CXCR3+耐药 B 细胞——而不是耐药性白血病细胞。这种模块化的化学方法为具有不同趋化因子特征的细胞群的实时免疫表型分析提供了一种通用策略,并将加速新的精准医学工具的设计,以推进血液肿瘤的个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/604c2cae8029/ja4c12035_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/ea25f2ee081c/ja4c12035_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/ecf4373002fe/ja4c12035_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/85e4a64dcd65/ja4c12035_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/604c2cae8029/ja4c12035_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/ea25f2ee081c/ja4c12035_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/ecf4373002fe/ja4c12035_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/85e4a64dcd65/ja4c12035_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f2/11544607/604c2cae8029/ja4c12035_0004.jpg

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J Am Chem Soc. 2024 Aug 14;146(32):22689-22698. doi: 10.1021/jacs.4c07286. Epub 2024 Aug 5.
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On-Demand Thio-Succinimide Hydrolysis for the Assembly of Stable Protein-Protein Conjugates.按需硫代琥珀酰亚胺水解法用于稳定的蛋白质-蛋白质偶联物的组装。
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Development of a Mature B Lymphocyte Probe through Gating-Oriented Live-Cell Distinction (GOLD) and Selective Imaging of Topical Spleen.
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Novel Fluorescent Strategy for Discriminating T and B Lymphocytes Using Transport System.利用转运系统区分T淋巴细胞和B淋巴细胞的新型荧光策略
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Inserting "OFF-to-ON" BODIPY Tags into Cytokines: A Fluorogenic Interleukin IL-33 for Real-Time Imaging of Immune Cells.将“关到开”型硼二吡咯(BODIPY)标签插入细胞因子:用于免疫细胞实时成像的荧光白细胞介素IL-33
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