Journal article

Improving the apo-state detergent stability of NTS1 with CHESS for pharmacological and structural studies

Daniel J Scott, Lutz Kummer, Pascal Egloff, Ross AD Bathgate, Andreas Plueckthun



The largest single class of drug targets is the G protein-coupled receptor (GPCR) family. Modern high-throughput methods for drug discovery require working with pure protein, but this has been a challenge for GPCRs, and thus the success of screening campaigns targeting soluble, catalytic protein domains has not yet been realized for GPCRs. Therefore, most GPCR drug screening has been cell-based, whereas the strategy of choice for drug discovery against soluble proteins is HTS using purified proteins coupled to structure-based drug design. While recent developments are increasing the chances of obtaining GPCR crystal structures, the feasibility of screening directly against purified GPCRs in ..

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Awarded by National Health and Medical Research Council of Australia

Awarded by Swiss National Science Foundation NCCR Structural Biology

Funding Acknowledgements

We acknowledge the professional help given by the staff of the Center for Microscopy and Image Analysis at the University of Zurich, where all FACS was performed, particularly Vinko Tosevski and Claudia Dumrese. Natasha Lam, The Florey Institute, is acknowledged for her assistance in conducting the saturation and competition binding assays. This work was supported by a C.J. Martin Biomedical Overseas Fellowship (520309) from the National Health and Medical Research Council of Australia and a postdoctoral fellowship from the Forschungskredit of the University of Zurich (both to DJ.S.). This project was funded by the Swiss National Science Foundation NCCR Structural Biology 51NF40-117226 and subsequent grant 31003A_153143 (both to AP).