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Updated: May 21, 2026

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
Published on: September 13, 2013
Recent Advances in GPCR Ligand Discovery Using DNA-Encoded Library Technology: From Affinity Binding to Functional
Ruolan Zhou1,2, Jiajia Wang1, Xiang Li3
1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
None:
DNA-encoded library (DEL) technology has emerged as a transformative platform for the discovery of bioactive small molecules against challenging therapeutic targets including G protein-coupled receptors (GPCRs). As a clinically pivotal class of membrane-bound targets, GPCRs pose inherent challenges in the discovery of novel ligands. This Microperspective highlights recent methodological advances (2015-2026) that enable DEL selections against GPCRs, thereby facilitating the identification of diverse ligand modalities, including agonists, antagonists, allosteric modulators, and biased ligands. Furthermore, we discuss current challenges and future directions in the application of DEL technology to GPCR drug discovery, with a specific emphasis on opportunities in receptor stabilization, selection strategy design, and computational method development.
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