在生物系统中,活性氧物种激活的生物对等化学反应,由酸盐中的二托特拉辛酶激活

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Dongqing Ming¹, Jiaxue Zhang¹, Binsong Mu¹

¹State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.

Nature communications

|February 10, 2026

概括

研究人员开发了一种由活性氧物种 (ROS) 激活的新生物对等反应. 这一突破使得有针对性的药物输送和生物系统中的蛋白质降解能够得到精确的控制,为疾病治疗提供了新的途径.

科学领域:

生物化学生物化学
化学生物学化学生物学
药用化学医学化学

背景情况:

生物对角化学对于生物和医学应用至关重要.
开发对生物触发物如反应性氧物种 (ROS) 产生响应的按需反应对于时空控制至关重要.
ROS与衰老和疾病有关,但ROS激活的生物对角结合仍然具有挑战性.

研究的目的:

开发一种新的ROS激活的生物对角四链接.
通过使用ROS作为触发器,使生物系统中反应的时空控制成为可能.
为了证明在向蛋白质降解和瘤选择性药物输送中的应用.

主要方法:

利用酸盐中的二托特拉,在暴露于过高的过氧化水平时在现场产生酸.
开发了一种针对蛋白质溶解的嵌合体 (PROTAC) 用于使用ROS激活结合来针对性降解含原蛋白4 (BRD4).
设计了一种瘤选择性药物递送系统,使用与转环子素结合的多克索鲁比辛,由ROS响应性结合激活.

主要成果:

成功建立了一个由活性氧物种 (ROS) 触发的四素结合系统.
通过使用 PROTAC 策略,证明了 ROS 触发的 BRD4 向降解.
在体外和体内实现了高效的瘤选择性输送多克索鲁比,超过现有方法.

结论:

开发的ROS响应的生物对等反应为生物应用提供了时空控制.
这一策略使得有针对性的蛋白质降解和精确的药物输送成为潜在的癌症治疗.
该系统对推进精准医学和研究疾病病原性有前途.

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