Regio-Selective Intramolecular Hydrogen/Deuterium Exchange in Gas-Phase Electron Transfer Dissociation

2017 ◽  
Vol 28 (5) ◽  
pp. 971-977 ◽  
Author(s):  
Yoshitomo Hamuro
Keyword(s):  
Electron Transfer ◽  
Gas Phase ◽  
Electron Transfer Dissociation ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Hydrogen Deuterium ◽  
Intramolecular Hydrogen

scholarly journals Analysis of phosphoinositide 3-kinase inhibitors by bottom-up electron-transfer dissociation hydrogen/deuterium exchange mass spectrometry

2017 ◽  
Vol 474 (11) ◽  
pp. 1867-1877 ◽  
Author(s):  
Glenn R. Masson ◽  
Sarah L. Maslen ◽  
Roger L. Williams
Keyword(s):  
Mass Spectrometry ◽  
Electron Transfer ◽  
Electron Transfer Dissociation ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Exchange Mass Spectrometry ◽  
Hydrogen Deuterium ◽  
Deuterium Exchange Mass Spectrometry ◽  
Phosphoinositide 3 Kinase ◽  
Hdx Ms

Until recently, one of the major limitations of hydrogen/deuterium exchange mass spectrometry (HDX-MS) was the peptide-level resolution afforded by proteolytic digestion. This limitation can be selectively overcome through the use of electron-transfer dissociation to fragment peptides in a manner that allows the retention of the deuterium signal to produce hydrogen/deuterium exchange tandem mass spectrometry (HDX-MS/MS). Here, we describe the application of HDX-MS/MS to structurally screen inhibitors of the oncogene phosphoinositide 3-kinase catalytic p110α subunit. HDX-MS/MS analysis is able to discern a conserved mechanism of inhibition common to a range of inhibitors. Owing to the relatively minor amounts of protein required, this technique may be utilised in pharmaceutical development for screening potential therapeutics.

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