Dopamine receptors are a key pharmaceutical target, and subtype D2R is a popular target for neurological disorders such as Parkinson’s disease and schizophrenia, and has been implicated in the etiology of autism. The ligand, dopamine, is a fundamental component of neuronal signaling, and functional dopamine receptors are also expressed on multiple cell types--suggesting its broad use as a signaling molecule in other organ systems. Unfortunately, dopamine receptors are challenging to study with traditional biochemical techniques, as they are membrane-bound, and extremely difficult to isolate and crystalize. Here, we develop new trifunctional probes that: 1) act as a functional D2 agonist, 2) crosslink to the D2 receptor,  and 3) provide a CuAAC handle for enrichment or labeling. These probes demonstrate the proof-of-concept for using the strength of pharmacophore-ligand interaction to drive the probe targeting to the dopamine D2 receptor, and have a number of immediate applications in determining dopamine receptor structure and proteomic targets of agonists in clinical use.

Dopamine receptor D2: Agonist-probes for structural analysis and activity profiling

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.