Collision induced unfolding and dissociation differentiates ATP-competitive from allosteric protein tyrosine kinase inhibitors

International Journal of Mass Spectrometry(2018)

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摘要
•Collision induced unfolding (CIU) revealing stark differences between allosteric and ATP-competitive Abl-kinase inhibitors.•Collision induced dissociation (CID) also seems to discriminate between these two classes of protein-inhibitor complexes.•A comparison of CIU and CID data reveals a greater range of CIU scores than for CID, reflecting the greater structural sensitivity of CIU.•CIU/CID analysis of Abl complexes formed using CHO-das, a hybrid inhibitor produces scores dissimilar to either allosteric or ATP-competitive inhibitors.•Hybrid CIU/CID analysis of Abl-inhibitor complexes is a promising method for future kinase inhibitor discovery efforts.
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关键词
Ion mobility,Protein kinases,Pharmaceuticals,Collisional activation,Native mass spectrometry
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