MALDI-FT-ICR

Easterling, M.L., Mize, T.H., and Amster, I. J., Routine part-per-million mass accuracy for high-mass ions space-charge effects in MALDI FT-ICR, Anal. Chem., 71, 624, 1999. 

Example Peptides often contain sulfur from cysteine. Provided there are at least two cysteines in the peptide molecule, the sulfur can be incorporated as thiol group (SH, reduced) or sulfur bridge (S-S, oxidized). Often, both forms are contained in the same sample. At ultrahigh-resolution, the contributions of these compositions to the same nominal m/z can be distinguished. The ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) FT-ICR mass spectrum of native and reduced [D-Pen jenkephalin gives an example of such a separation (Fig. 3.25). [39] The left expanded view shows fully resolved peaks due to and C2 isotopomers of the native and the all- C peak of the reduced compound at m/z 648. The right expansion reveals the peak of the native plus the... 

Fig. 3.25. Ultrahigh-resolution MALDI-FT-ICR mass spectrum of native (S-S) and reduced (2 X SH) [D-Pen ]enkephalin. The expanded m/z views of the second and third isotopic peak show fully mass-resolved signals. Reproduced from Ref. [39] with permission. American Chemical Society, 1997.

The MALDI-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (MALDI-FT-ICR-MS) and MALDI-Quadrupole-Ion-trap-TOF Mass Spectrometry (MALDI-QIT-TOF-MS) can be used on IMS. The FT-ICR-MS could provide the high resolution, expansive mass range and high sensitivity imaging MS data and good for determining the elemental composition of small molecules [60],... 

The MALDI-MS instrumentation used for IMS included MALDI-TOF, MALDI-Q-TOF, MALDI-TOF-TOF, MALDI-Q-Ion Mobility-TOFMS (MALDI-Q-IM-TOFMS) [113-117], MALDI-FT-ICR-MS, MALDI-Ion Trap [73, 118-120], and MALDI-QIT-TOF [121],... 

The ES/MALDI-FT-ICR mass spectrometer of the Institute of Organic Chemistry at the University of Tubingen is from Bruker Daltonik GmbH, Bremen. The system is evacuated by efficient turbo molecular pumps which allows HPLC and GC coupling over long time periods. ES, NanoSpray and MALDI ionization sources allow individual adaptation to particular problems. Samples from combinatorial chemistry can be routinely analyzed with the 60°-ESI from Analytica of Branford Inc. (Branford, MA) via LC/ES-FT-ICR-MS as well as small amounts of valuable biological samples with nanoESI. 

Fig. 10.13 2D-PAGE Separation of a cryoglobulin isolated from serum of a patient with glomerulonephritis (left) and MALDI-FT-ICR-MS of tryptic in-gel digest mixture of spot 7...

Peptide mass fingerprinting can be performed by use of MALDI-FT-ICR [94,95]. For example, Przybylski and co-woikers applied MALDI-FT-ICR to the proteomic analysis of cryoglobulins from a hepatitis C patient [96], and to alveolar proteomics associated with proteinosis and cystic fibrosis [97]. Alternatively, LC can be coupled with ESI FT-ICR for peptide mass fingerprinting [94]. Among other applications, LC coupled with ESI-FT-ICR has been used in the proteomic analysis of Escherichia coli [98], the proteomic analysis of amniotic fluid [99], the identification of brain natriuritic peptide (BNP-32) in plasma following heart failure [100], and in the molecular differentiation of ischemic and valvular heart disease [101]. 

Methods incorporating FT-ICR MS/MS have been applied also to bottom-up proteomic analyes. Hakansson et al. [66] applied ESI FT-ICR and IRMPD MS/MS to the analysis of glycoproteins isolated from human cerebrospinal fluid. Brock and co-workers [103] combined MALDI FT-ICR with SORI-CID. The throughput of this approach is hampered by the timescales associated with SORI-CID. Laskin and co-workers [104] compared approaches utilizing SORI-CID and SID coupled to ESI. The protein identification scores were comparable for the two techniques. SID has the advantage that no pump-down delay is needed and, therefore, more cycles of MS/ MS can be completed. 

Horn, D.M. Peters, E.C. Klock, H. Meyers, A. Brock, A. Improved protein identification using automated high mass measurement accuracy MALDI FT-ICR MS peptide mass fingerprinting. Int. J. Mass Spectrom. 2004, 238(2), 189-196. 

Van der Flage and co-workers [280] combined MALDI and Fourier transform ion cyclotron mass spectrometry (FT-ICR-MS) for the characterisation of polyoxyalkyleneamines. MALDI FT-ICR-MS was used to resolve intact, sodium ion cationised oligomer ions in the mass range from m/z 500 to 3500. NMR was used to measure the average end-group distribution to provide insight into conformational differences. In this respect, FT-ICR-MS and NMR data were complementary. Combined results yielded detailed information about chemical composition distributions of polyalkyleneamines that hitherto it was not possible to obtain with either technique separately. Merits and limitations of the data produced with MALDI FT-ICR-MS are discussed and compared with those of H and C NMR data [280]. 

Becker, J. S., Zoriy, M., Krause-Buchholz, U., Becker, J. S., Pickhardt, C., Przybylski, M., Pompe, W., Roedel, G. (2004) In-gel screening of phosphorus and copper, zinc and iron in proteins of yeast mitochondria by LA-ICP-MS and identification of phosphory-lated protein structures by MALDI-FT-ICR-MS after separation with two-dimensional gel electrophoresis. J Anal At Spectrom, 19, 1236-1243. 

Combined with electrospray ionization or MALDI, FT-ICR-MS is a very attractive tool for gas-phase studies of biomolecules such as peptides and proteins, oligonucleotides, and oligosaccharides. The possibihty to trap ions for prolonged periods of time, even up to thousands of seconds, can be applied in the study of gas-phase ion-molecule reactions. Application of proton-transfer reactions in ICR cells in the study of biomolecules has been reviewed [97]. Detailed structural as well as conformational studies on biomolecules rely on H/D-exchange experiments, for which FT-ICR is an excellent tool, e.g., [98, 99]. 

Fourier transform ion cyclotron resonance (FT-ICR, Chap. 4.7) is much betto" suited for laser desorption [5,6]. Best results are obtained when the ions are generated in an external ion source and subsequently transferred into the ICR cell for mass analysis [213]. MALDI-FT-ICR has become a mature combination [214,215]. Modem MALDI-FT-ICR instmments make use of collisional cooling of the plasma plume before transferring the ions into the ICR cell [216,217]. 

Figure 2.6 shows a MALDI-FT-ICR-MS spectrum of an ethylene oxide-propylene oxide copolymer in broadband mode. For this spectrum, the trapping delay was optimised to be 900 ps for maximum signal-to-noise ratio (S/N) at the centre of the MWD, i.e., it was not compensated for the flight-time-induced mass discrimination. The spectrum is the sum of the spectra of 250 consecutive laser shots. The expansion of the mass scale shows that the resolution is sufficient to resolve the naturally occurring isotopes of a component molecule. For example, the resolution in broadband mode (m/dml gy is 15000, with an S/N of 330 at mIz 969.6. 

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