Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 56, Issue 46, Pages 14463-14468Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201704849
Keywords
desorption; electrospray ionisation; G-protein coupled receptors; mass spectrometry; membrane protein complexes
Categories
Funding
- ERC Advanced Grant ENABLE [641317]
- MRC Programme Grant [G1000819]
- Wellcome Trust Investigator Award [104633/Z/14/Z]
- Royal commission for the Exhibition of 1851 fellowship
- Wellcome Trust [201505/Z/16/Z]
- Wellcome Trust
- MRC [G1000819, MC_PC_15029] Funding Source: UKRI
- Medical Research Council [G1000819, MC_PC_15029] Funding Source: researchfish
- Wellcome Trust [104633/Z/14/Z] Funding Source: researchfish
- European Research Council (ERC) [641317] Funding Source: European Research Council (ERC)
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Mass spectrometry (MS) applications for intact protein complexes typically require electrospray (ES) ionization and have not been achieved via direct desorption from surfaces. Desorption ES ionization (DESI) MS has however transformed the study of tissue surfaces through release and characterisation of small molecules. Motivated by the desire to screen for ligand binding to intact protein complexes we report the development of a native DESI platform. By establishing conditions that preserve non-covalent interactions we exploit the surface to capture a rapid turnover enzyme-substrate complex and to optimise detergents for membrane protein study. We demonstrate binding of lipids and drugs to membrane proteins deposited on surfaces and selectivity from a mix of related agonists for specific binding to a GPCR. Overall therefore we introduce this native DESI platform with the potential for high-throughput ligand screening of some of the most challenging drug targets including GPCRs.
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