High-field fourier transform ion cyclotron resonance mass spectrometry for simultaneous trapping and gas-phase hydrogen/deuterium exchange of peptide ions

Gas-phase hydrogen/deuterium exchange of D₂O with M + H]⁺ ions of angiotensin II, angiotensin I, Sar¹]-angiotensin II, bradykinin, des-Arg¹-bradykinin, des-Arg⁹-bradykinin, luteinizing hormone releasing hormone (LH-RH), and substance P has been examined by Fourier transform ion cyclotron resonance mass spectrometry at 9.4 tesla. Because the FTICR dynamic range increases quadratically with magnetic field, parent ions from a mixture of several peptides may be confined simultaneously for long periods at high pressure (e.g., 1 h at 1 × 10⁻⁵ torr) without quadrupolar axialization (and its attendant ion heating), for faster data acquisition and better controlled comparisons between different peptides. A high magnetic field also facilitates stored waveform inverse Fourier transform (SWIFT) isolation of monoisotopic M + H]⁺ parent ions, so that deuterium incorporation patterns may be determined directly without the need for isotopic distribution deconvolution. Finally, a higher magnetic field provides for a greatly extending trapping period, for measurement of much slower rates. Angiotensin I, angiotensin II, and Sar¹]-angiotensin II are found to undergo a rapid exchange. Angiotensin II and Sar¹]-angiotensin II exhibit multiple deuterium uptake distributions, corresponding to multiple gas-phase conformations. In contrast, substance P exchanges slowly and LH-RH displays no observable exchange. Comparison of the relative H/D exchange rates for bradykinin and its des-Arg-derivatives supports the hypothesis that bradykinin adopts a folded gas-phase conformation that unfolds upon removal of either terminal arginine residue.