RAPID GAS-PHASE ISOTOPIC LABELING FOR ENHANCED DETECTION OF PROTEIN CONFORMATIONS

摘要

A mass spectrometer (MS)that is adapted to allow rapid gas- phasehy-drogen/deuterium exchange (HDX) labelingof ions in one or more traveling wave ionguides (TWIGs) with or without ionmobili-ty separation. The addition of isotopiclabel-ing by gas- phase HDX offers a sensitiveal-ternative dimension for conformationalde-tection, which enables high resolutionde-tection of gaseous conformations based onshape and surface reactivity. Gas-phase,iso-topic HDX labeling, or "curtain" labeling,can be performed by infusing a reactive,iso-topic labeling gas, e.g., ND3, into one ormore of the traveling-ion wave guides(TWIG) in the MS. Analyte ions retained inthe potential wells of a traveling wavegen-erated by one or more of the TWIGs can beisotopic labeled at adjustable gas pressures.Labeling times can also be controlled byad-justing the speed of the traveling wave andcan be performed within milliseconds ofionizations, probing protein conformationspresent in solution.