Restricted accessResearch articleFirst published online 2018-07
Development of a Cannabinoid-Based Photoaffinity Probe to Determine the Δ 8/9 -Tetrahydrocannabinol Protein Interaction Landscape in Neuroblastoma Cells
Δ9-Tetrahydrocannabinol (THC), the principle psychoactive ingredient in Cannabis, is widely used for its therapeutic effects in a large variety of diseases, but it also has numerous neurological side effects. The cannabinoid receptors (CBRs) are responsible to a large extent for these, but not all biological responses are mediated via the CBRs.
Objectives:
The identification of additional target proteins of THC to enable a better understanding of the (adverse) physiological effects of THC.
Methods:
In this study, a chemical proteomics approach using a two-step photoaffinity probe is applied to identify potential proteins that may interact with THC.
Results:
Photoaffinity probe 1, containing a diazirine as a photocrosslinker, and a terminal alkyne as a ligation handle, was synthesized in 14 steps. It demonstrated high affinity for both CBRs. Subsequently, two-step photoaffinity labeling in neuroblastoma cells led to identification of four potential novel protein targets of THC. The identification of these putative protein hits is a first step towards a better understanding of the protein interaction profile of THC, which could ultimately lead to the development of novel therapeutics based on THC.
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