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Marvin L. Vestal

Bio: Marvin L. Vestal is an academic researcher from Applied Biosystems. The author has contributed to research in topics: Mass spectrometry & Time-of-flight mass spectrometry. The author has an hindex of 32, co-authored 76 publications receiving 3981 citations. Previous affiliations of Marvin L. Vestal include University of California, San Francisco & Northeastern University.


Papers
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Journal ArticleDOI
TL;DR: A new matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time- of-flight (TOF/TOF) high-resolution tandem mass spectrometer is described for sequencing peptides.
Abstract: A new matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) high-resolution tandem mass spectrometer is described for sequencing peptides. This instrument combines the advantages of high sensitivity for peptide analysis associated with MALDI and comprehensive fragmentation information provided by high-energy collision-induced dissociation (CID). Unlike the postsource decay technique that is widely used with MALDI-TOF instruments and typically combines as many as 10 separate spectra of different mass regions, this instrument allows complete fragment ion spectra to be obtained in a single acquisition at a fixed reflectron voltage. To achieve optimum resolution and focusing over the whole mass range, it may be desirable to acquire and combine three separate sections. Different combinations of MALDI matrix and collision gas determine the amount of internal energy deposited by the MALDI process and the CID process, which provide control over the extent and nature of the fr...

529 citations

Journal ArticleDOI
TL;DR: In this article, a matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer system is described, which provides dramatically improved performance over that obtained with identical TOF analyzers operated with constant electrical fields.
Abstract: A new delayed extraction matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer system is described which provides dramatically improved performance over that obtained with identical TOF analyzers operated with constant electrical fields In this system the ions formed by MALDI are produced in a weak electrical field, and subsequently extracted by application of a high voltage pulse after a predetermined time delay Three parameters can be independently adjusted to optimize the performance These include the field magnitude and direction during and immediately following ion production, the magnitude of the extraction field, and the time delay between the laser pulse and application of the extraction field Theoretical equations are presented which guide the selection of these parameters to optimize the performance Results are presented from three TOF analyzers of similar design, but ranging in size from a 13 m linear analyzer to a 64 m reflector In all cases delayed extraction provides substantially improved resolution over that obtained from static operation In the smallest linear analyzer resolution of M/ΔM (full width at half maximum) of 4000 is demonstrated for angiotensin I, and with the largest reflecting analyzer, the isotope peaks of bovine insulin are resolved nearly to baseline With larger proteins, the isotopic peaks are not resolved, but resolution approaching the width of the isotopic envelope is obtained Resolution improvement is demonstrated for proteins up to 30 kDa In addition to improved resolution, delayed extraction is shown to improve the quality of MALDI mass spectra by suppressing matrix background, reducing chemical noise, and minimizing the effect of laser intensity on performance

492 citations

Patent
10 Apr 1998
TL;DR: In this paper, a time-of-flight mass spectrometer for measuring the mass-to-charge ratio of a sample molecule is described, which provides independent control of the electric field experienced by the sample before and during ion extraction.
Abstract: A time-of-flight mass spectrometer for measuring the mass-to-charge ratio of a sample molecule is described. The spectrometer provides independent control of the electric field experienced by the sample before and during ion extraction. Methods of mass spectrometry utilizing the principles of this invention reduce matrix background, induce fast fragmentation, and control the transfer of energy prior to ion extraction.

212 citations

Journal ArticleDOI
TL;DR: The present method detected errors in published sequences and was able to develop sequences from peptides differing in mass by one dalton, showing both the power of the present approach and the need for using de novo methods more frequently than may be otherwise appreciated.

188 citations

Journal ArticleDOI
TL;DR: A delayed ion extraction technique is shown to dramatically improve mass resolution and the overall quality of matrix-assisted laser desorption ionization (MALDI) mass spectra of oligonucleotides, and fast fragmentation taking place between the ionizing pulse and the extraction pulse is demonstrated to be a sequencing tool for small oligon nucleotides.
Abstract: A delayed ion extraction technique is shown to dramatically improve mass resolution and the overall quality of matrix-assisted laser desorption ionization (MALDI) mass spectra of oligonucleotides. Isotope limited mass resolution was obtained on samples up to 10-kDa molecular mass in linear mode, and as high as 7500 mass resolution (defined at half peak height) was observed in reflector mode. This performance is as good as that achieved to date for peptides and proteins. Applications included the detection of oxidized byproducts of phosphorothioate DNA and separation of components differing only by 15 Da at 9.5-kDa molecular mass. In addition to single components, complex mixtures could also be analyzed at greatly improved performance over conventional MALDI. An example is shown for sequence verification of an oligonucleotide of 31 bases in length by analyzing the failure products. Mass accuracy was adequate to verify sequences of oligodeoxyribonucleotides up to 9500-Da molecular mass. Fast fragmentation t...

159 citations


Cited by
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Journal ArticleDOI
13 Mar 2003-Nature
TL;DR: The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.
Abstract: Recent successes illustrate the role of mass spectrometry-based proteomics as an indispensable tool for molecular and cellular biology and for the emerging field of systems biology. These include the study of protein-protein interactions via affinity-based isolations on a small and proteome-wide scale, the mapping of numerous organelles, the concurrent description of the malaria parasite genome and proteome, and the generation of quantitative protein profiles from diverse species. The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.

6,597 citations

Journal ArticleDOI
14 Apr 2006-Science
TL;DR: Recent advances in mass spectrometry instrumentation are reviewed in the context of current and emerging research strategies in protein science.
Abstract: Mass spectrometry is a central analytical technique for protein research and for the study of biomolecules in general. Driven by the need to identify, characterize, and quantify proteins at ever increasing sensitivity and in ever more complex samples, a wide range of new mass spectrometry-based analytical platforms and experimental strategies have emerged. Here we review recent advances in mass spectrometry instrumentation in the context of current and emerging research strategies in protein science.

1,992 citations

Journal ArticleDOI
TL;DR: Stable isotope labeling strategies in combination with mass spectrometry have been applied successfully to study the dynamics of modifications and hold tremendous potential to map modification sites in molecular detail.
Abstract: Post-translational modifications modulate the activity of most eukaryote proteins. Analysis of these modifications presents formidable challenges but their determination generates indispensable insight into biological function. Strategies developed to characterize individual proteins are now systematically applied to protein populations. The combination of function- or structure-based purification of modified 'subproteomes', such as phosphorylated proteins or modified membrane proteins, with mass spectrometry is proving particularly successful. To map modification sites in molecular detail, novel mass spectrometric peptide sequencing and analysis technologies hold tremendous potential. Finally, stable isotope labeling strategies in combination with mass spectrometry have been applied successfully to study the dynamics of modifications.

1,933 citations

Journal ArticleDOI
TL;DR: This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.
Abstract: The function of many of the uncharacterized openreadingframesdiscoveredbygenomicsequencingcanbe determined at the level of expressed gene products, the proteome.However,identifyingthecognategenefromminute amounts of protein has been one of the major problems in molecularbiology.Usingyeastasanexample,wedemonstrate here that mass spectrometric protein identification is a generalsolutiontothisproblemgivenacompletelysequenced genome. As a first screen, our strategy uses automated laser desorption ionization mass spectrometry of the peptide mix- tures produced by in-gel tryptic digestion of a protein. Up to 90% of proteins are identified by searching sequence data bases by lists of peptide masses obtained with high accuracy. The remaining proteins are identified by partially sequencing several peptides of the unseparated mixture by nanoelectro- spray tandem mass spectrometry followed by data base searchingwithmultiplepeptidesequencetags.Inblindtrials, themethodledtounambiguousidentificationinallcases.In the largest individual protein identification project to date, a total of 150 gel spots—many of them at subpicomole amounts—were successfully analyzed, greatly enlarging a yeast two-dimensional gel data base. More than 32 proteins were novel and matched to previously uncharacterized open reading frames in the yeast genome. This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.

1,456 citations

Journal ArticleDOI
TL;DR: 4. Automated Interpretation of CID Spectra 282 5. Accurate Mass Tags 282 C. Protein Identification in Complex Mixtures 282 D. Analysis of Protein Expression 284 III.
Abstract: 4. Automated Interpretation of CID Spectra 282 5. Accurate Mass Tags 282 C. Protein Identification in Complex Mixtures 282 D. Analysis of Protein Expression 284 III. Proteomes and Post-Translational Modifications 285 A. Proteomes 285 1. The Analytical Challenge 285 2. Analysis of Protein−Protein Complexes 286 B. Post-Translational Modifications 286 1. Background 286 2. Detection and Purification of Phosphoproteins 288

1,416 citations