Despite its promising role in the active control of biological functions by light, photocaging remains untested in acetylcholinesterase (AChE), a key enzyme in the cholinergic family. Here, we describe synthesis, photochemical properties and biochemical activities of two caged oxime compounds applied in the photocontrolled reactivation of the AChE inactivated by reactive organophosphate. Each of these consists of a photocleavable coumarin cage tethered to a known oxime reactivator for AChE that belongs in an either 2-(hydroxyimino)acetamide or pyridiniumaldoxime class. Of these, the first caged compound was able to successfully go through oxime uncaging upon irradiation at long-wavelength ultraviolet light (365 nm) or visible light (420 nm). It was further evaluated in AChE assays in vitro under variable light conditions to define its activity in the photocontrolled reactivation of paraoxon-inactivated AChE. This assay result showed its lack of activity in the dark but its induction of activity under light conditions only. In summary, this article reports a first class of light-activatable modulators for AChE and it offers assay methods and novel insights that help to achieve an effective design of caged compounds in the enzyme control.

中文翻译：

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设计用于乙酰胆碱酯酶再激活的光控制的笼式肟再激活器†

尽管光笼在通过光主动控制生物功能方面发挥着积极作用，但在胆碱能家族中的关键酶乙酰胆碱酯酶 (AChE) 中，光笼仍然未经测试。在这里，我们描述了两种笼状肟化合物的合成、光化学性质和生化活性，这些化合物用于光控活化被活性有机磷酸酯灭活的 AChE。这些中的每一个都由一个可光裂解的香豆素笼组成，该笼拴在一个已知的 AChE 肟再激活剂上，它属于 2-(羟基亚氨基)乙酰胺或吡啶鎓醛肟类。其中，第一个笼状化合物能够在长波长紫外光（365 nm）或可见光（420 nm）的照射下成功地通过肟解笼。在体外AChE 测定中对其进行了进一步评估在可变光照条件下确定其在对氧磷灭活的 AChE 的光控再激活中的活性。该测定结果显示其在黑暗中缺乏活性，但仅在光照条件下诱导活性。总之，本文报道了第一类 AChE 的光激活调节剂，它提供了有助于实现酶控制中笼状化合物的有效设计的测定方法和新见解。