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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Rapid Communications in Mass Spectrometry 9 (1995), S. 644-650 
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: A new approach, bio-affinity characterization mass spectrometry (BACMS), aimed at providing a more rapid, sensitive and potentially more flexible alternative to techniques presently employed for the characterization of noncovalent interactions in mixtures, such as would be encountered in combinatorial chemistry, is presented. BACMS avoids some of the difficulties and potential artifacts associated with affinity chromatography since the noncovalent associations occur in solution; thus, BACMS avoids the requirement of solid support media and the development of non-interfering linker species. This paper describes the conceptual basis for the methodology and its potential use in applications which include the screening of high affinity ligands in support of new drug development. BACMS exploits new Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry technologies which, when coupled to electrospray ionization (ESI), allow the investigation of specific noncovalent complexes formed in solution. BACMS utilizes the well-known attributes of FTICR, such as the high resolution mass analysis and (MS)n (n ≥ 2) capabilities; however, it is even more directly a result of recently developed techniques involving quadrupolar excitation, such as selected-ion accumulation. These tools are demonstrated and the results illustrate the extraordinary sensitivity achievable (solution concentrations of 1 × 10-9 M without the use of separations prior to ESI). Thus, the new capabilities demonstrated here, in conjunction with ESI, will be useful for the investigation of very low relative concentration noncovalent association directly from solution, and promote a faster alternative for combinatorial mixture screening and analysis.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: The occurrence of small shifts in the cyclotron frequency during the acquisition of very long transients (in excess of 80 s) has been observed to be a limiting factor for ultrahigh-resolution mass measurements of protein ions performed with electrospray-ionization Fourier-transform ion-cyclotron-resonance mass spectrometry. Resolution measurements were restricted to values less than 106 because of the frequency shifts. Measurements of the frequency shifts, performed by sequentially transforming small segments of the transient, allowed the shift to be characterized and fitted to a 4th-order equation. The sampling rate of the acquired transient was then modulated (at a rate equal to the reciprocal of the rate for the frequency shift) to allow ultrahigh resolution, greater than 2 × 106, and improved mass measurement and precision to be achieved for a small protein.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: The coupling of an electrospray ionization (ESI) source to a Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer provides a facility for the high resolution, accurate mass analysis of large biopolymers. Typically the m/z range of the electrosprayed ions injected and trapped in the FTICR cell is between m/z 500 and 2500 (but can vary considerably with solution conditions). Recent reports on quadrupole excitation have demonstrated the ability to cool the magnetron motion of ions trapped in the FTICR mass spectrometer cell by converting this motion to cyclotron motion which, under appropriate pressure conditions, damps readily to the center of the cell. The use of a broadband waveform (swept frequency or stored waveform inverse Fourier-transform) for the quadrupole cooling pulse was shown to provide cooling of a wide range of m/z ions, while implementation of a single frequency demonstrated a much narrower m/z response. This report demonstrates the successful combination of single-frequency quadrupole cooling with external injection of electrosprayed ions into an FTICR mass spectrometer for m/z selected-ion accumulation. This capability is particularly significant with electrospray ionization since it allows ions of only one charge state to be accumulated in the cell, and greatly increases the potential dynamic range of ESI-FTICR.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1076-5174
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: An electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometer has been used in conjunction with the technique of selected-ion accumulation (SIA) to investigate its utility for the study of the gas phase behavior of noncovalent complexes from solution. SIA is demonstrated to provide the selective accumulation of weakly bound species, providing a significant enhancement in the attainable signal-to-noise ratio and dynamic range. The frequency response of quadrupole excitation was first determined by selectively accumulating single charge states of large, highly adducted, highly charged molecules such as bovine albumin and bovine albumin dimer. Under the conditions employed, the response (selective accumulation) was found to be as narrow as 500 Hz. Additionally the SIA was found to be sufficiently gentle to allow accumulation of both specific and nonspecific weak noncovalent complexes, such as the myoglobin-heme complex observed in basic solutions and complexes of myoglobin and single amino acids, such as tryptophan. This result is probably due to the continual application of quadrupole excitation during the high pressure accumulation event, preventing any significant growth of magnetron motion, and subsequently, allowing interconversion to form only small cyclotron radii. We also demonstrate the simultaneous application of SIA with dipolar sustained off-resonance irradiation (SORI) during the ion accumulation period so as to allow selective accumulation of dissociation products. The SIA/SORI combination promises to greatly extend (MS)n capabilities by allowing the selective accumulation of any dissociation product in any step along a given dissociation pathway.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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