Targeting peptide G protein-coupled receptors (GPCRs) for novel drug development

The largest single class of drug targets is the G Protein-Coupled Receptor (GPCR) family, which were targets for ~30% of prescription drugs sold in the USA in 2010. However current drugs only target a small proportion of the GPCR family and peptide GPCRs, although showing great potential as targets for treating many diseases, are poorly targeted with drugs. Modern GPCR drug development is encumbered by a lack of information about the molecular structure underlying GPCR function and the reliance on cell-based assays that are prone to false positives in drug screening.

While the past 10 years have seen advances in our knowledge of GPCR structures peptide GPCRs, especially those with large structured ectodomains (ECDs), remain poorly understood.


  • Target peptide GPCRs for novel drug development

A main issue with studying GPCRs is the flexibility of linkers joining the ECDs to the transmembrane domains (TMDs) which impedes crystallisation. Hence the study of complex peptide receptors requires different approaches.

Our laboratory targets peptide GPCRs for drug development utilising state-of-the-art molecular pharmacology, biochemical and Nuclear magnetic resonance (NMR) techniques. These techniques enable us to map the native peptide binding sites of these receptors and determine the mechanisms of receptor activation as well their cell signalling characteristics. A complete understanding of the mechanism of ligand binding and activation is required to design drugs targeting these receptors.

Furthermore, we are utilising novel protein engineering techniques that enable these normally highly unstable proteins to be produced and purified for structural studies using advanced protein NMR techniques, crystallography and Cryo-EM (also see projects from Associate Professor Daniel Scott). Our studies are complemented by peptide drug development projects and small molecule screening projects with collaborators.

Additionally, we are working with pharmaceutical industry partners (eg. Takeda and Novartis) to facilitate drug development efforts. Honours, Masters and PhD projects are available on multiple GPCR targets with training in various techniques as outlined above.

Research team


Professor Paul Gooley – Department of Biochemistry and Pharmacology, University of Melbourne

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If you’re interested in learning more about this project please contact our team.

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