G protein-coupled receptors (GPCRs) represent the largest fraction of the druggable proteome. However, due to the hydrophobic nature of GPCRs, predicting fine structure under crystallographic conditions is challenging. Thus, there remains a critical need to study GPCR structure and function under physiological conditions. To address this issue, we have developed a set of modular photoaffinity ligands for the human dopamine D2 receptor based on existing modulators. Herein, we report on the pharmacological activity of these probes, degree of photoreactivity, target selectivity, and proteomic analysis to map the active site of dopamine D2. Our findings help to enhance our understanding of the dynamic structure of dopamine D2 and create a new avenue for rational structure-based drug design.

Interacting with interactions: Mapping the human dopamine D2 receptor using clickable photoaffinity ligands

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.