An introduction to electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry: Essential tools in a modern biotechnology environment

The tremendous progress in biochemistry and biotechnology has been made possible in part by recent advances in analytical methods, in particular mass spectrometry. With the introduction of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI), mass spectrometry allowed the determination of the molecular weight of peptides and proteins with a much greater accuracy than achievable by traditional methods such as SDS-PAGE and biogel chromatography. In addition, these mass spectrometry experiments have become routine and can be performed within minutes. ESI and MALDI (in combination with enzymatic methods) can also provide vital structural data such as the amino acid sequence and the sites of posttranslational modifications for peptides and proteins with a sensitivity that competes favorably with other methods. The use of ESI and MALDI is not limited to peptides and proteins; analysis of oligonucleotides and oligosaccharides has been simplified by these techniques as well. For information about structurally significant noncovalent interaction between various types of biomolecules, ESI is probably one of the most convenient methods. Not surprisingly, we anticipate that the mass spectrometers with these ionization capabilities will soon become standard equipment in all pharmaceutical and biotechnology laboratories. © 1997 John Wiley & Sons, Inc. Biospectroscopy 3: 259–280, 1997

[1]  R. Henderson,et al.  Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B7 determined by mass spectrometry and computer modeling. , 1993, Journal of immunology.

[2]  R. Anderegg,et al.  Conformation of cytochrome c studied by deuterium exchange-electrospray ionization mass spectrometry. , 1994, Analytical chemistry.

[3]  A. Shevchenko,et al.  Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry , 1996, Nature.

[4]  A Sette,et al.  Definition of specific peptide motifs for four major HLA-A alleles. , 1994, Journal of immunology.

[5]  C. G. Edmonds,et al.  Tandem mass spectrometry of very large molecules: serum albumin sequence information from multiply charged ions formed by electrospray ionization. , 1991, Analytical chemistry.

[6]  Klaus Biemann,et al.  Amino acid sequencing of proteins , 1994 .

[7]  C. Sutton,et al.  Peptide mass fingerprinting of chaperonin‐containing TCP‐1 (CCT) and copurifying proteins , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  P. Kebarle,et al.  From ions in solution to ions in the gas phase - the mechanism of electrospray mass spectrometry , 1993 .

[9]  B. Chait,et al.  Heat-induced conformational changes in proteins studied by electrospray ionization mass spectrometry. , 1993, Analytical chemistry.

[10]  B. Ganem,et al.  Recognition of cell‐wall peptide ligands by vancomycin group antibiotics: Studies using ion spray mass spectrometry , 1995 .

[11]  C. Fenselau,et al.  Surfaces for interfacing protein gel electrophoresis directly with mass spectrometry , 1995 .

[12]  T. Hunkapiller,et al.  Peptide mass maps: a highly informative approach to protein identification. , 1993, Analytical biochemistry.

[13]  B. Ganem,et al.  Detection of oligonucleotide duplex forms by ion-spray mass spectrometry , 1993 .

[14]  B. Ganem,et al.  Studies of non-covalent interactions of actinomycin D with single-stranded oligodeoxynucleotides by ion spray mass spectrometry and tandem mass spectrometry. , 1994, Biological mass spectrometry.

[15]  P. Traldi,et al.  MS/MS applications in biological problems , 1993 .

[16]  J. Yates,et al.  Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. , 1995, Analytical chemistry.

[17]  C. Fenselau,et al.  Poly(vinylidene difluoride) membranes as the interface between laser desorption mass spectrometry, gel electrophoresis, and in situ proteolysis , 1994 .

[18]  C. Watanabe,et al.  Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Yates,et al.  An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database , 1994, Journal of the American Society for Mass Spectrometry.

[20]  F. McLafferty,et al.  Mass spectrometry of macromolecules: has its time now come? , 1994, Annual review of biophysics and biomolecular structure.

[21]  C. Cantor,et al.  A strategy for rapid and efficient DNA sequencing by mass spectrometry , 1996, Nature Biotechnology.

[22]  M. Qian,et al.  Peptide Mapping by CNBr Degradation on a Nitrocellulose Membrane with Analysis by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry , 1995 .

[23]  E. Hoffmann.  Tandem mass spectrometry: A primer , 1996 .

[24]  F. McLafferty,et al.  Sequence Information from 42−108-mer DNAs (Complete for a 50-mer) by Tandem Mass Spectrometry , 1996 .

[25]  S. Carr,et al.  Selective detection and sequencing of phosphopeptides at the femtomole level by mass spectrometry. , 1996, Analytical biochemistry.

[26]  Stephen A. Martin,et al.  Identification of the facile gas-phase cleavage of the Asp-Pro and Asp-Xxx peptide bonds in matrix-assisted laser desorption time-of-flight mass spectrometry. , 1993, Analytical chemistry.

[27]  Y. Konishi,et al.  Conformational stability of heme proteins in vacuo. , 1994, Biochemistry.

[28]  J. Henion,et al.  Capillary electrophoresis-atmospheric pressure ionization mass spectrometry for the characterization of peptides. Instrumental considerations for mass spectrometric detection. , 1991, Journal of chromatography.

[29]  Richard D. Smith,et al.  Noncovalent Complexes of Nucleic Acids and Proteins Studied by Electrospray Ionization Mass Spectrometry , 1996 .

[30]  V. Katta,et al.  Conformational changes in proteins probed by hydrogen-exchange electrospray-ionization mass spectrometry. , 1991, Rapid communications in mass spectrometry : RCM.

[31]  D. Pappin,et al.  Peptide ladder sequencing by mass spectrometry using a novel, volatile degradation reagent. , 1994, Rapid communications in mass spectrometry : RCM.

[32]  L. Deterding,et al.  Capillary liquid chromatography/mass spectrometry , 1994 .

[33]  B. Shushan,et al.  Characterization of the tryptic map of recombinant DNA derived tissue plasminogen activator by high-performance liquid chromatography-electrospray ionization mass spectrometry. , 1991, Analytical chemistry.

[34]  Richard D. Smith,et al.  Carbonic Anhydrase-Inhibitor Binding: From Solution to the Gas Phase , 1997 .

[35]  P. Rudd,et al.  Examination of complex oligosaccharides by matrix‐assisted laser desorption/ionization mass spectrometry on time‐of‐flight and magnetic sector instruments , 1994 .

[36]  Robert J. Cotter,et al.  Matrix-assisted laser desorption/ionization of noncovalently bound compounds , 1995 .

[37]  V. Katta,et al.  Hydrogen/Deuterium Exchange Electrospray Ionization Mass Spectrometry: A Method for Probing Protein Conformational Changes in Solution , 1993 .

[38]  R. Cotter,et al.  Time-of-flight mass spectrometry for the structural analysis of biological molecules. , 1992, Analytical chemistry.

[39]  F. McLafferty,et al.  Attomole Protein Characterization by Capillary Electrophoresis-Mass Spectrometry , 1996, Science.

[40]  B. Reinhold,et al.  Carbohydrate molecular weight profiling, sequence, linkage, and branching data: ES-MS and CID. , 1995, Analytical chemistry.

[41]  B. Day,et al.  Reduction of phenoxyl radicals by thioredoxin results in selective oxidation of its SH-groups to disulfides. An antioxidant function of thioredoxin. , 1995, Biochemistry.

[42]  Michael Karas,et al.  Matrix‐assisted laser desorption ionization mass spectrometry , 1991 .

[43]  S. N. Davey,et al.  The rapid identification of intact microorganisms using mass spectrometry , 1996, Nature Biotechnology.

[44]  W. Hancock,et al.  Characterization of humanized anti-TAC, an antibody directed against the interleukin 2 receptor, using electrospray ionization mass spectrometry by direct infusion, LC/MS, and MS/MS. , 1994, Analytical chemistry.

[45]  M. Karas,et al.  Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. , 1988, Analytical chemistry.

[46]  G. Ciliberto,et al.  Anti‐inflammatory actions of an N‐terminal peptide from human lipocortin 1 , 1993, British journal of pharmacology.

[47]  Capillary electrophoresis/mass spectrometry , 1993 .

[48]  F. McLafferty,et al.  Attomole-sensitivity electrospray source for large-molecule mass spectrometry. , 1995, Analytical chemistry.

[49]  D. Deforce,et al.  Analysis of DNA adducts in DNA hydrolysates by capillary zone electrophoresis and capillary zone electrophoresis-electrospray mass spectrometry. , 1996, Analytical chemistry.

[50]  W. Geraerts,et al.  Structural Elucidation of a Peptide from a Single Neuron by Matrix-Assisted Laser Desorption/Ionization Employing a Tandem Double-Focusing Magnetic-Orthogonal Acceleration Time-of-Flight Mass Spectrometer , 1997 .

[51]  B. Karger,et al.  Capillary electrophoresis/electrospray ionization mass spectrometry: improvement of protein detection limits using on-column transient isotachophoretic sample preconcentration , 1993 .

[52]  C. Fenselau,et al.  Sequencing electroblotted proteins by tandem mass spectrometry. , 1995, Rapid communications in mass spectrometry : RCM.

[53]  C. Dobson,et al.  Probing the Nature of Noncovalent Interactions by Mass Spectrometry. A Study of Protein−CoA Ligand Binding and Assembly , 1996 .

[54]  B. Chait,et al.  Observation of the heme-globin complex in native myoglobin by electrospray-ionization mass spectrometry , 1991 .

[55]  H. M. Geysen,et al.  Isotope or mass encoding of combinatorial libraries. , 1996, Chemistry & biology.

[56]  R N Hayes,et al.  Collision-induced dissociation. , 1990, Methods in enzymology.

[57]  B. Chait,et al.  Protein ladder sequencing. , 1993, Science.

[58]  J. Yates,et al.  Mining genomes: correlating tandem mass spectra of modified and unmodified peptides to sequences in nucleotide databases. , 1995, Analytical chemistry.

[59]  R. Bradshaw,et al.  Application of combined mass spectrometry and partial amino acid sequence to the identification of gel‐separated proteins , 1996, Electrophoresis.

[60]  B. Chait,et al.  Weighing naked proteins: practical, high-accuracy mass measurement of peptides and proteins. , 1992, Science.

[61]  A. Peter Snyder.  Biochemical and biotechnological applications of electrospray ionization mass spectrometry : developed from a symposium sponsored by the Division of Analytical Chemistry at the 209th National Meeting of the American Chemical Society, Anaheim, California, April 2-6, 1995 , 1995 .

[62]  M. Fitzgerald,et al.  Mass spectrometry of nucleic acids: the promise of matrix-assisted laser desorption-ionization (MALDI) mass spectrometry. , 1995, Annual review of biophysics and biomolecular structure.

[63]  G. Becker,et al.  Protein mass spectrometry: applications to analytical biotechnology. , 1995, Journal of chromatography. A.

[64]  Francis M. Wampler,et al.  Coexisting stable conformations of gaseous protein ions. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[65]  T. Baillie.  Advances in the application of mass spectrometry to studies of drug metabolism, pharmacokinetics and toxicology* , 1992 .

[66]  R. Whittal,et al.  Analysis of Single Mammalian Cell Lysates by Mass Spectrometry , 1996 .

[67]  M. Glocker,et al.  Electrospray Mass Spectrometry of Biomacromolecular Complexes with Noncovalent Interactions—New Analytical Perspectives for Supramolecular Chemistry and Molecular Recognition Processes , 1996 .

[68]  I. Papayannopoulos,et al.  The interpretation of collision‐induced dissociation tandem mass spectra of peptides , 1996 .

[69]  S. Carr,et al.  Phosphopeptide analysis by matrix-assisted laser desorption time-of-flight mass spectrometry. , 1996, Analytical chemistry.

[70]  J. J. Conboy,et al.  Atmospheric pressure ionization mass spectrometry. Detection for the separation sciences. , 1990 .

[71]  E. Nordhoff.  Matrix-assisted laser desorption/ionization mass spectrometry as a new method for the characterization of nucleic acids , 1996 .

[72]  R. Yost,et al.  Tandem mass spectrometry: quadrupole and hybrid instruments. , 1990, Methods in enzymology.

[73]  The analysis of mock DNA sequencing reactions using matrix‐assisted laser desorption/ionization mass spectrometry , 1993 .

[74]  Jimmy K. Eng,et al.  Tutorial review. Future prospects for the analysis of complex biological systems using micro-column liquid chromatography–electrospray tandem mass spectrometry , 1996 .

[75]  C. Dobson,et al.  Detection of transient protein folding populations by mass spectrometry. , 1993, Science.

[76]  R. Bakhtiar,et al.  Electrospray Ionization Mass Spectrometry: Part III: Applications in Inorganic Chemistry and Synthetic Polymer Chemistry , 1996 .

[77]  L. Hood,et al.  Structural analysis of proteins by capillary HPLC electrospray tandem mass spectrometry , 1991 .

[78]  J. Yates,et al.  Direct analysis and identification of proteins in mixtures by LC/MS/MS and database searching at the low-femtomole level. , 1997, Analytical chemistry.

[79]  T. Keough,et al.  GENERATION AND SCREENING OF COMBINATORIAL PEPTIDE LIBRARIES DESIGNED FOR RAPID SEQUENCING BY MASS SPECTROMETRY , 1995 .

[80]  D. Kirsch,et al.  Sequenching of peptides in a time-of-flight mass spectrometer: evaluation of postsource decay following matrix-assisted laser desorption ionisation (MALDI) , 1994 .

[81]  R. Levis.  Laser desorption and ejection of biomolecules from the condensed phase into the gas phase. , 1994, Annual review of physical chemistry.

[82]  J. Henion,et al.  LC/MS and LC/MS/MS determination of protein tryptic digests , 1990, Journal of the American Society for Mass Spectrometry.

[83]  Kermit K. Murray,et al.  DNA sequencing by mass spectrometry. , 1996, Journal of mass spectrometry : JMS.

[84]  M. Gross.  Mass spectrometry in the biological sciences : a tutorial , 1992 .

[85]  R. Colton,et al.  Electrospray mass spectrometry applied to inorganic and organometallic chemistry , 1995 .

[86]  M. Vestal,et al.  Applications of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry to oligonucleotide analysis. , 1996, Analytical chemistry.

[87]  L. Wennogle,et al.  Characterization of SH2-ligand interactions via library affinity selection with mass spectrometric detection. , 1996, Biochemistry.

[88]  P. Griffin,et al.  Microchemical structural determination of a peptoid covalently bound to a polymeric bead by matrix-assisted laser desorption ionization time-of-flight mass spectrometry , 1994 .

[89]  J. Stults.  Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). , 1995, Current opinion in structural biology.

[90]  C. Fenselau,et al.  Chemical aspects of fast atom bombardment , 1987 .

[91]  F. McLafferty,et al.  Mass Spectrometry: Recent Advances and Future Directions , 1996 .

[92]  M. Wilm,et al.  Analytical properties of the nanoelectrospray ion source. , 1996, Analytical chemistry.

[93]  Stephen A. Martin,et al.  Mass spectrometric determination of the amino acid sequence of peptides and proteins , 1987 .

[94]  A. Dell,et al.  High sensitivity collisionally-activated decomposition tandem mass spectrometry on a novel quadrupole/orthogonal-acceleration time-of-flight mass spectrometer. , 1996, Rapid communications in mass spectrometry : RCM.

[95]  C. Dobson,et al.  Conformation of GroEL-bound α-lactalbumin probed by mass spectrometry , 1994, Nature.

[96]  L. Sheng,et al.  Polymer analysis by photons, sprays, and mass spectrometry , 1994 .

[97]  C. Dobson,et al.  Cooperative Elements in Protein Folding Monitored by Electrospray Ionization Mass Spectrometry , 1995 .

[98]  R. Anderegg,et al.  Probing the helical content of growth hormone-releasing factor analogs using electrospray ionization mass spectrometry , 1993, Journal of the American Society for Mass Spectrometry.

[99]  J. J. Moreno,et al.  In vitro and in vivo effects of the anti-inflammatory peptides, antiflammins. , 1992, Biochemical pharmacology.

[100]  Zhongqi Zhang,et al.  Probing noncovalent structural features of proteins by mass spectrometry , 1994 .

[101]  T. Keough,et al.  Matrix-assisted laser desorption ionization for rapid determination of the sequences of biologically active peptides isolated from support-bound combinatorial peptide libraries. , 1994, Rapid communications in mass spectrometry : RCM.

[102]  J. Raff.  Biological mass spectrometry, present and future , 1995 .

[103]  J. Loo.  Teaching Editorial - Bioanalytical Mass Spectrometry: Many Flavors to Choose , 1995 .

[104]  P. Højrup,et al.  Rapid identification of proteins by peptide-mass fingerprinting , 1993, Current Biology.

[105]  B. Ganem,et al.  Characterization of benzodiazepine "combinatorial" chemical libraries by on-line immunoaffinity extraction, coupled column HPLC-ion spray mass spectrometry-tandem mass spectrometry. , 1996, Analytical chemistry.

[106]  W. Hancock,et al.  Reversed-phase peptide mapping of glycoproteins using liquid chromatography/electrospray ionization-mass spectrometry. , 1996, Methods in enzymology.

[107]  A. Agulnik,et al.  Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein. , 1995, Science.

[108]  S. Martin,et al.  DNA sequencing by delayed extraction-matrix-assisted laser desorption/ionization time of flight mass spectrometry. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[109]  P. Lansbury,et al.  Peptide Models of a Hydrophobic Cluster at the C-Terminus of the Beta-Amyloid Protein , 1994 .

[110]  G. Neubauer,et al.  Parent ion scans of unseparated peptide mixtures. , 1996, Analytical chemistry.

[111]  S. Ceman,et al.  Invariant chain peptides in most HLA-DR molecules of an antigen-processing mutant. , 1992, Science.

[112]  M. Mann,et al.  Electrospray ionization for mass spectrometry of large biomolecules. , 1989, Science.

[113]  I. Stewart,et al.  Developments in the electrospray mass spectrometry of inorganic species , 1996 .

[114]  R. Aebersold,et al.  High‐sensitivity determination of tyrosine‐phosphorylated peptides by on‐line enzyme reactor and electrospray ionization mass spectrometry , 1995, Protein science : a publication of the Protein Society.

[115]  B. Ganem,et al.  Detection of noncovalent receptor-ligand complexes by mass spectrometry , 1991 .

[116]  J. Greef,et al.  Strategies in developing interfaces for coupling liquid chromatography and mass spectrometry , 1991 .

[117]  J. Yates,et al.  The quadrupole ion trap mass spectrometer--a small solution to a big challenge. , 1997, Analytical biochemistry.

[118]  P. Derrick,et al.  Comparison of Novel Sampling Methods for the Analysis of Capillary Electrophoresis Fractions by Matrix‐assisted Laser Desorption/Ionization Time‐of‐flight Mass Spectrometry , 1997 .

[119]  Richard D. Smith,et al.  High performance fourier transform ion cyclotron resonance mass spectrometric detection for capillary electrophoresis , 1996 .

[120]  Friedrich Lottspeich,et al.  Matrix-assisted laser desorption ionization mass spectrometry of proteins electroblotted after polyacrylamide gel electrophoresis , 1994 .

[121]  B. Karger,et al.  Free Solution Identification of Candidate Peptides from Combinatorial Libraries by Affinity Capillary Electrophoresis/Mass Spectrometry , 1995 .

[122]  Stephen A. Martin,et al.  Delayed extraction matrix‐assisted laser desorption time‐of‐flight mass spectrometry , 1995 .

[123]  J R Yates,et al.  Protein structure analysis by mass spectrometry. , 1996, Methods in enzymology.

[124]  Francis M. Wampler,et al.  Gas-phase folding and unfolding of cytochrome c cations. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[125]  C. Cotman,et al.  Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. , 1992, The Journal of biological chemistry.

[126]  Terry D. Lee,et al.  Analysis of peptide mixtures by capillary high performance liquid chromatography: A practical guide to small‐scale separations , 1992, Protein science : a publication of the Protein Society.

[127]  D. Koshland,et al.  Determination of in Vivo Phosphorylation Sites in Protein Kinase C (*) , 1995, The Journal of Biological Chemistry.

[128]  F. Regnier,et al.  C-terminal ladder sequencing via matrix-assisted laser desorption mass spectrometry coupled with carboxypeptidase Y time-dependent and concentration-dependent digestions. , 1995, Analytical chemistry.

[129]  G. Siuzdak.  The emergence of mass spectrometry in biochemical research. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[130]  J. Henion,et al.  Recent developments in electrospray mass spectrometry including implementation on an ion trap. , 1993, Journal of pharmaceutical and biomedical analysis.