A "Three-in-One" Multifunctional Probe for Bcl-2/Mcl-1 Profiling and Visualizingin Situ
A "Three-in-One" Multifunctional Probe for Bcl-2/Mcl-1 Profiling and Visualizingin Situ
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用于 Bcl-2/Mcl-1 原位分析和可视化的“三合一”多功能探针
DOI：
10.1002/cbic.202000441
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发表时间：
2021
期刊：
影响因子：
3.2
通讯作者：
Zhang Zhichao
中科院分区：
文献类型：
--
作者：
Zhang Xiaodong;Wang Ziqian;Guo Zongwei;Song Ting;He Nianzhe;Zhu Junjie;Cao Keke;Zhang Zhichao
BCL-2和Mcl-1是抗细胞凋亡蛋白家族中的两个分支，被认为是细胞凋亡的关键调节因子和肿瘤的有效治疗靶点。然而，没有一种小分子探针能够同时在 原位分析和显示Bcl2和Mcl-1。在这里，我们报道了一种多功能分子探针(BnN3-OPD-ALK)，采用三位一体的分子设计策略，将Bcl2/Mcl-1结合配体、荧光报告基和光反应基叠氮基整合到同一支架中。BnN3-OPD-ALK与Bcl2/Mcl-1呈亚微摩尔亲和力，呈亮绿色自发荧光。并成功地应用于 体外和细胞内Bcl2/Mcl-1的标记、捕获、富集化和生物成像。该策略有助于对双基因Bcl2/Mcl-1相关疾病的准确早期诊断和有效治疗。
Bcl‐2 and Mcl‐1, the two arms of the anti‐apoptotic Bcl‐2 family proteins, have been identified as key regulators of apoptosis and effective therapeutic targets of cancer. However, no small‐molecular probe is capable of profiling and visualizing both Bcl‐2 and Mcl‐1 simultaneouslyin situ. Herein, we report a multifunctional molecular probe (BnN3‐OPD‐Alk) by a “three‐in‐one” molecular designing strategy, which integrated the Bcl‐2/Mcl‐1 binding ligand, fluorescent reporter group and photoreactive group azido into the same scaffold. BnN3‐OPD‐Alk exhibited sub‐micromolar affinities to Bcl‐2/Mcl‐1 and bright green self‐fluorescence. It was then successfully applied for Bcl‐2/Mcl‐1 labeling, capturing, enriching, and bioimaging bothin vitroand in cells. This strategy could facilitate the precise early diagnosis and effective therapy of dual Bcl‐2/Mcl‐1‐related diseases.