Validation of ion mobility spectrometry ‐ mass spectrometry as a screening tool to identify type II kinase inhibitors of FGFR1 kinase
نویسندگان
چکیده
Rationale The protein kinase FGFR1 regulates cellular processes in human development. As over-activity of is implicated with cancer, effective inhibitors are demand. Type I inhibitors, which bind to the active form FGFR1, less than type II inactive form. Screening distinguish between and required. Methods X-ray crystallography was used indicate whether a range potential or conformation. binding affinity each ligand measured using biochemical methods. Electrospray ionisation - ion mobility spectrometry mass (ESI-IMS-MS) conjunction collision-induced unfolding generated conformational profile FGFR1–ligand complex. results that protein's depends on inhibitor II. Results confirmed kinase. Collision-induced combined ESI-IMS-MS showed distinct differences folding landscape for inhibitors. Biochemical studies indicated similar affinities both types thus providing confidence variations detected can be interpretated unequivocally this an screening method. Conclusions A robust method has been implemented mode by monitoring FGFR1. This rapid requires low sample concentrations could as high-throughput technique characterisation novel
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ژورنال
عنوان ژورنال: Rapid Communications in Mass Spectrometry
سال: 2021
ISSN: ['1097-0231', '0951-4198']
DOI: https://doi.org/10.1002/rcm.9130