GPCR

We are especially interested in small molecule drugs that can modulate G protein-coupled receptors (GPCR) activated by proteins and peptides (e.g. Tyndall et al, Chem. Rev. 2005). Our chemistry researchers design and develop potent and selective non-peptide agonists and antagonists and study the molecular basis for agonist and antagonist activities. Our pharmacologists investigate the effects of our novel compounds on intracellular signaling pathways and in animal models of inflammatory, metabolic, cardiovascular and other diseases. We design biased ligands and harness their properties to obtain greater control over therapeutic profiles (e.g. Blakeney et al, Chem. Rev. 2007).

GPCRs in General: Selected Publications

Crystal Structures of Protein-Bound Cyclic Peptides. Malde AK, Hill TA, Iyer A, Fairlie DP. Chem Rev 2019, 119, 9861-9914.

Orally Absorbed Cyclic Peptides. Nielsen DS, Shepherd NE, Xu W, Lucke AJ, Stoermer MJ, Fairlie DP. Chem Rev. 2017, 117, 8094-8128.

Matching Cavities in G Protein-Coupled Receptors to Infer Ligand-Binding Sites. Madala PK, Fairlie DP, Bodén M. J Chem Inf Model 2012, 52, 1401-1410.

Update 1 of: Over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure. Ruiz-Gómez G, Tyndall JD, Pfeiffer B, Abbenante G, Fairlie DP. Chem Rev. 2010, 110(4), PR1-41.

Nonpeptidic ligands for peptide-activated G protein-coupled receptors. Blakeney JS, Reid RC, Le GT, Fairlie DP. Chem Rev. 2007, 107(7), 2960-3041.

Nonpeptide ligands that target peptide-activated GPCRs in inflammation. Blakeney JS, Fairlie DP. Curr Med Chem. 2005, 12(25), 3027-3042.

Over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure. Tyndall JD, Pfeiffer B, Abbenante G, Fairlie DP. Chem Rev. 2005, 105(3), 793-826. [>100 citations]

Complement GPCRs: Recent Publications

Ras-related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis, and chemokine secretion in human macrophages. Wu KC, Condon ND, Hill TA, Reid RC, Fairlie DP, Lim J. J Innate Immunity 2023, 15, 468-484.

Potent thiophene antagonists of human complement C3a receptor with anti-inflammatory activity. Rowley JA, Reid RC, Poon EKY, Wu KC, Lim J, Lohman RJ, Hamidon JK, Yau MK, Halili MA, Durek T, Iyer A, Fairlie DP. J Med Chem 2020, 63, 529-541.

Complement C3a and C5a receptors promote GVHD by suppressing mitophagy in recipient dendritic cells. Nguyen H, Kuril S, Bastian D, Kim J, Zhang M, Vaena SG, Dany M, Dai M, Heinrichs JL, Daenthanasanmak A, Iamsawat S, Schutt S, Fu J, Wu Y, Fairlie DP, Atkinson C, Ogretmen B, Tomlinson S, Yu XZ. JCI Insight 2018, 3(24). pii: 121697.

Chemical Approaches To Modulating Complement-Mediated Diseases. Iyer A, Xu W, Reid RC, Fairlie DP. J Med Chem 2018, 61, 3253-3276.

The ribosomal protein S19 suppresses antitumor immune responses via the complement C5a receptor 1. Vadrevu SK, Sharma SK, Chintala NK, Cho J-H, Patel J, Patel B, Fairlie DP, Paterson Y, Astrinidis A, Karbowniczek M, Markiewski MM. J Immunol 2017, 198, 2989-2999.

Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a. Lohman R-J, Hamidon JK, Reid RC, Rowley JA, Yau M-K, Halili MA, Nielsen DS, Lim J, Wu K-C, Loh Z, Do A, Suen JY, Iyer A, Fairlie DP. Nature Commun 2017, 8, 351.

Europium-Labeled Synthetic C3a Protein as a Novel Fluorescent Probe for Human Complement C3a Receptor. Dantas de Araujo A, Wu C, Wu KC, Reid RC, Durek T, Lim J, Fairlie DP. Bioconjug Chem 2017, 28, 1669-1676.

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