Good news! Catch as catch can! 😄
"... The CATCH method involves the insertion of tiny chemical handles into drug molecules. These distinct chemical handles don’t react with anything else in the body, but do allow the addition of fluorescent tags after the drug molecules have bound to their targets. In part because human or animal tissue tends to diffuse and block the light from these fluorescent tags, Ye and his team combined the tagging process with a technique that makes tissue relatively transparent.
In this initial study, the researchers optimized and evaluated their method for “covalent drugs,” which bind irreversibly to their targets with stable chemical bonds known as covalent bonds. This irreversibility of binding makes it particularly important to verify that such drugs are hitting their intended targets. ..."
From the abstract:
"The lack of tools to observe drug-target interactions at cellular resolution in intact tissue has been a major barrier to understanding in vivo drug actions. Here, we develop clearing-assisted tissue click chemistry (CATCH) to optically image covalent drug targets in intact mammalian tissues. CATCH permits specific and robust in situ fluorescence imaging of target-bound drug molecules at subcellular resolution and enables the identification of target cell types. Using well-established inhibitors of endocannabinoid hydrolases and monoamine oxidases, direct or competitive CATCH not only reveals distinct anatomical distributions and predominant cell targets of different drug compounds in the mouse brain but also uncovers unexpected differences in drug engagement across and within brain regions, reflecting rare cell types, as well as dose-dependent target shifts across tissue, cellular, and subcellular compartments that are not accessible by conventional methods. CATCH represents a valuable platform for visualizing in vivo interactions of small molecules in tissue."
In situ identification of cellular drug targets in mammalian tissue (no public access)
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