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双生物标志物靶向探针实现金黄色葡萄球菌的信号开启型表面标记。

A dual biomarker-targeting probe enables signal-on surface labeling of Staphylococcus aureus.

机构信息

Department of Chemical Biology, College of Chemistry and Chemical Engineering, the Key Laboratory for Chemical Biology of Fujian Province, State Key Laboratory for Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, China.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, China.

出版信息

Bioorg Med Chem Lett. 2023 Sep 1;93:129428. doi: 10.1016/j.bmcl.2023.129428. Epub 2023 Aug 2.

Abstract

Imaging or killing of a specific pathogen is of significance for precise therapy. Staphylococcus aureus (S. aureus) is an infectious gram-positive bacteria relying on Sortase A (SrtA) to anchor cell surface protein on peptidoglycan. We herein report signal-on labeling of S. aureus with self-quenched optical probes featuring vancomycin-conjugated SrtA substrate that is flanked by a dabcyl moiety paired with either fluorescein or eosine photosensizer (PS). SrtA-mediated cleavage of the substrate motif releases the dabcyl quencher, leading to covalent labeling of peptidoglycan with fluorescein or PS of restored photophysical property. The dual biomarked-enabled peptidoglycan labeling enables signal-on imaging and effective photodynamic destruction of S. aureus, suggesting a protheranostic approch activatable to SrtA-positive bacteria engaged in myriad diseases.

摘要

对特定病原体的成像或杀灭对于精准治疗具有重要意义。金黄色葡萄球菌(S. aureus)是一种感染性革兰氏阳性细菌,依靠 Sortase A(SrtA)将细胞表面蛋白锚定在肽聚糖上。本文报告了使用具有万古霉素偶联 SrtA 底物的自猝灭光学探针对金黄色葡萄球菌进行信号放大标记的方法,该底物侧翼是带有 dabcyl 部分的肽,与荧光素或曙红光敏剂(PS)配对。SrtA 介导的底物模体的切割释放出 dabcyl 猝灭剂,导致肽聚糖与荧光素或 PS 的共价标记,恢复光物理性质。双重生物标记的肽聚糖标记能够实现金黄色葡萄球菌的信号放大成像和有效光动力破坏,提示了一种针对参与多种疾病的 SrtA 阳性细菌的前治疗方法。

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