Tandem time-of-flight (TOF/TOF) mass spectrometry and the curved-field reflectron.
The curved-field reflectron (CFR), when used as the second mass analyzer in a tandem time-of-flight mass spectrometer, provides a design that enables the use of very high energy collision-induced dissociation (CID). Specifically, this is because the wide energy bandwidth of the CFR obviates the need for floating the collision region to decelerate the precursor ions and subsequently reaccelerating product ions to enable reflectron focusing. Here we describe the evolution of tandem instruments based on the CFR, from its introduction in 1993 to the current commercial TOF(2) mass spectrometer from Shimadzu Corporation, and briefly review the history of TOF/TOF instruments. A number of applications are also described. One is the characterization of a C-terminal cleavage of cystatin C that appears to be associated with patients with remitting relapse multiple sclerosis (RRMS). Both surface-enhanced laser desorption/ionization (SELDI) and MALDI were used on a high performance TOF instrument operating in the MS and MS/MS modes. Tandem TOF mass spectrometry has also been used to determine the acetylation sites on histones and on the enzyme, histone acetyl transferase (HAT), responsible for the modification. Acetylation has been determined quantitatively for multiple sites on histone H3 and H4 using a deuteroacetylation method. For a number of closely spaced sites on the histone tail regions, MS/MS enables us to then determine both the order and distribution of acetylation.
Cotter
Robert J
RJ
Middle Atlantic Mass Spectrometry Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. rcotter@jhmi.edu
Griffith
Wendell
W
Jelinek
Christine
C
D000107:Acetylation; D000595:Amino Acid Sequence; D055316:Cystatin C; D015891:Cystatins / Q000737:chemistry; D006657:Histones / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000175:diagnosis; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000295:instrumentation* / Q000379:methods
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D006657:Histones; D010455:Peptides; D011506:Proteins