A theranostic abscisic acid-based molecular glue.
A theranostic abscisic acid-based molecular glue.
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DOI：
10.1039/d2sc06995d
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发表时间：
2023-03-22
期刊：
影响因子：
8.4
通讯作者：
中科院分区：
文献类型：
--
作者：
分子胶能够选择性地控制特定蛋白质对或蛋白质组之间的相互作用以及相关的下游效应，已成为操纵细胞功能和开发人类疾病新疗法的有前途的策略。具有诊断和治疗能力的治疗诊断学在疾病部位起作用，已成为高精度同时实现这两种功能的有力工具。为了选择性地激活分子胶在所需的网站，并在同一时间监测激活信号，在这里，我们报告了一个前所未有的治疗诊断模块化分子胶平台集成信号传感/报告和化学诱导邻近（CIP）的策略。我们首次证明了在同一平台上将成像和激活能力与分子胶集成在一起，以创建治疗诊断分子胶。通过一个独特的氨基甲酰基肟连接基团将近红外荧光团二氰基亚甲基-4H-吡喃（DCM）与CIP诱导剂脱落酸（阿坝）偶联，合理设计了一种治疗诊断分子胶ABA-Fe（ii）-F1。我们还设计了一种新版本的ABA-CIP，具有增强的配体响应灵敏度。我们已经验证了治疗诊断分子胶可以感测Fe 2+并产生用于监测的开启NIR荧光，以及释放活性诱导配体以控制细胞功能，包括基因表达和蛋白质易位。这种新的分子胶策略为构建具有治疗诊断能力的新型分子胶的研究和生物医学应用铺平了道路。一种基于ABA的治疗诊断分子胶，能够感测Fe（II）和触发阿坝和NIR荧光团的释放，已被开发用于时空监测和操纵细胞功能。
Molecular glues, capable of selectively controlling the interactions between specific pairs or groups of proteins and the associated downstream effects, have become a promising strategy for manipulating cellular functions and developing novel therapies for human diseases. Theranostics with both diagnostic and therapeutic capabilities acting at disease sites has become a powerful tool to achieve both functions simultaneously with high precision. To selectively activate molecular glues at the desired site and monitor the activation signals at the same time, here we report an unprecedented theranostic modular molecular glue platform integrating signal sensing/reporting and chemically induced proximity (CIP) strategies. We have demonstrated for the first time the integration of imaging and activation capacity with a molecular glue on the same platform to create a theranostic molecular glue. A theranostic molecular glue ABA-Fe(ii)-F1 was rationally designed by conjugating a NIR fluorophore dicyanomethylene-4H-pyran (DCM) with a CIP inducer abscisic acid (ABA) using a unique carbamoyl oxime linker. We have also engineered a new version of ABA-CIP with an enhanced ligand-responding sensitivity. We have validated that the theranostic molecular glue can sense Fe2+ and produce turn-on NIR fluorescence for monitoring as well as releasing the active inducer ligand to control cellular functions including gene expression and protein translocation. This novel molecular glue strategy paves the way to building a new class of molecular glues with theranostic capacity for research and biomedical applications. A theranostic ABA-based molecular glue, capable of sensing Fe(ii) and triggering the release of ABA and NIR fluorophores, has been developed for spatiotemporal monitoring and manipulating cellular functions.
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影响因子：
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通讯作者：
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