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Mass Spectrometry in the Characterization of Variant Hemoglobins

  • Chapter
Mass Spectrometry

Part of the book series: Modern Analytical Chemistry ((MOAC))

Abstract

About 150 million people throughout the world carry abnormal hemoglobins, with consequences ranging from trivial to lethal. More than one in 800 people have hemoglobins that differ from normal by amino acid substitutions, globin chain elongations, contractions, and fusions. In determining this incidence, the most common ones—variants Hb S, Hb E, and Hb C—were not included (1).

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References

  1. Bunn, H. F., and Forget, B. G., 1986, Hemoglobin: Molecular, Genetic and Clinical Aspects, W. B. Saunders Co., Philadelphia.

    Google Scholar 

  2. The figure for number of individuals worldwide with abnormal hemoglobins is approximate and was generated by Dr. William P. Winter.

    Google Scholar 

  3. Kim, H. C., Atwater, J., and Schwartz, E., 1983, Separation of hemoglobins, in Hematology 3rd ed. (W. J. Williams, E. Beutler, A. J. Ersley, and M. A. Lichtman, eds.), McGraw-Hill, New York, pp. 1611–1619.

    Google Scholar 

  4. Schneider, R. G., and Barwick, R. C., 1982, Hemoglobin mobility in citrate agar electro-phoresis—its relationship to anion binding, Hemoglobin 6:199–208.

    Article  CAS  Google Scholar 

  5. Basset, P., Beuzard, Y., Garel, M. C., and Rosa, J., 1978, Isoelectric focusing of human hemoglobin: its application to screening, to the characterization of 70 variants, and to the study of modified fractions of normal hemoglobins, Blood 51:971–982.

    CAS  Google Scholar 

  6. Loomis, S. J., Go, M., Kupeli, L., Bartling, D. J., and Binder, S. R., 1990, An automated system for sickle cell screening, Am. Clin. Lab. Oct.:33-40.

    Google Scholar 

  7. Alter, B. P., Goff, S. C., Efremov, G. D., Gravely, M., and Huisman, T. H. J., 1980, Globin chain electrophoresis: A new approach to the determination of the Gγ/Aγ ratio in fetal haemoglobin and to studies of globin synthesis, Br. J. Haematol. 44:527–534.

    Article  CAS  Google Scholar 

  8. Rochette, J., Righetti, P. G., Bosisio, A. B., Vertongen, F., Schneck, G., Boissel, J. P., Labie, D., and Wajcman, H., 1984, Immobilized pH gradients and reversed-phase high-performance liquid chromatography: A strategy for characterization of haemoglobin variants with electrophoretic mobility identical to that of Hb A., J. Chromatog. 285:143–152.

    Article  CAS  Google Scholar 

  9. Whitney III, J. B., Cobb, R. R., Popp, R. A., and O’Rourke, T. W., 1985, Detection of neutral amino acid substitutions in proteins, Proc. Natl. Acad. Sci. U.SA. 82:7647–7650.

    Article  Google Scholar 

  10. Castagnola, M., Dobosz, M., Landolfi, R., Pascali, V. L., De Angelis, F., Vettore, L., and Perona, G., 1988, Determination of neutral haemoglobin variants by immobilized pH gradient, reversed-phase high-performance liquid chromatography and fast-atom bombardment mass spectrometry: the case of a Hb Torino α43 (CEI) Phe→Val, Biol. Chem. Hoppe—Seyler 369:241–246.

    Article  CAS  Google Scholar 

  11. Shelton, J. B., Shelton, J. R., and Schroeder, W. A., 1981, Further experiments in the separation of globin chains by high performance liquid chromatography, J. Liquid Chromatog. 4:1381–1392.

    Article  CAS  Google Scholar 

  12. Green, B. N., Oliver, R. W. A., Falick, A. M., Shackleton, C. H. L., Roitman, E., and Witkowska, H. E., 1991, Electrospray MS, LSIMS and MS/MS for the rapid detection and characterization of variant hemoglobins, in Biological Mass Spectrometry (A. L. Burlingame and J. A. McCloskey, eds.), Elsevier, Amsterdam, pp. 129–146.

    Google Scholar 

  13. Ingram, V. M., 1956, A specific chemical difference between the globins of normal human and sickle-cell anemia haemoglobin, Nature 178:792–794.

    Article  CAS  Google Scholar 

  14. Ingram, V. M., 1958, Abnormal human haemoglobins. I. The comparison of normal human and sickle-cell haemoglobins by “fingerprinting,” Biochim. Biophys. Acta 28:539–545.

    Article  CAS  Google Scholar 

  15. Schroeder, W. A., Jones, R. T., Cormick, J., and McCalla, K., 1962, Chromatographic separation of peptides on ion exchange resins. Separation of peptides from enzymatic hydrolyzates of the α, ′, and γ chains of human hemoglobins, Anal. Chem. 34:1570–1575.

    Article  CAS  Google Scholar 

  16. Wilson, J. B., Lam, H., Pravatmuang, P., and Huisman, T. H. J., 1979, Separation of tryptic peptides of normal and abnormal α, ′, γ, and δ hemoglobin chains by high-performance liquid chromatography, J. Chromatog. 179:271–290.

    Article  CAS  Google Scholar 

  17. Matsuo, T., Matsuda, H., Katakuse, L, Wada, Y., Fujita, T., and Hayashi, A., 1981, Field desorption mass spectra of tryptic peptides of human hemoglobin chains, Biomed. Mass Spectrom. 8:25–30.

    Article  CAS  Google Scholar 

  18. Wada, Y., Hayashi, A., Fujita, T., Matsuo, T., Katakuse, I., and Matsuda, H., 1983, Structural analysis of human hemoglobin variants by mass spectrometry, Int. J. Mass Spectrom. Ion Phys. 48:209–212.

    Article  CAS  Google Scholar 

  19. Wada, Y., Hayashi, A., Masanori, F., Katakuse, I., Ichihara, T., Nakabushi, H., Matsuo, T., Sakurai, T., and Matsuda, H., 1983, Characterization of a new fetal hemoglobin variant, Hb F Izumi AγGlu→Gly, by molecular secondary ion mass spectrometry, Biochim. Biophys. Acta 749:244–248.

    Article  CAS  Google Scholar 

  20. Hayashi, A., Wada, Y., Matsuo, T., Katakuse, I., and Matsuda, H., 1987, Neonatal screening and mass-spectrometric analysis of hemoglobin variants in Japan, Acta haemat. 78:114–118.

    Article  CAS  Google Scholar 

  21. Pucci, P., Carestia, C., Fioretti, G., Mastrobuoni, A. M., and Pagano, L., 1985, Protein fingerprint by fast atom bombardment mass spectrometry: Characterization of normal and variant human haemoglobins, Biochem. Biophys. Res. Commun. 130:84–90.

    Article  CAS  Google Scholar 

  22. Rahbar, S., Lee, T. D., Baker, J. A., Rabinowitz, L. T., Asmerom, Y., Legesse, K., and Ranney, H. M., 1986, Reverse phase high-performance liquid chromatography and secondary ion mass spectrometry. A strategy for identification of ten human hemoglobin variants, Hemoglobin 10:379–400.

    Article  CAS  Google Scholar 

  23. Castagnola, M., Landolfi, R., Rossetti, D. V., De Angelis, F., and Ceccarelli, S., 1986, Determination of abnormal hemoglobins by the combined use of reversed-phase high performance liquid chromatography and fast atom bombardment mass spectrometry, Anal. Lett. 19:1793–1807.

    Article  CAS  Google Scholar 

  24. Promé, D., Promé, J.-C., Blouquit, Y., Lacombe, C., Rosa, J., and Robinson, J. D., 1987, FAB mapping of proteins: Detection of mutation sites in abnormal human hemoglobins, Spectros. Int. J. 5:157–170.

    Google Scholar 

  25. Promé, D., Promé, J.-C., Pratbernou, F., Blouquit, Y., Galacteros, F., Lacombe, C., Rosa, J., and Robinson, J. D., 1988, Identification of some abnormal haemoglobins by fast atom bombardment mass spectrometry and fast atom bombardment tandem mass spectrometry, Biomed. Environ. Mass Spec. 16:41–44.

    Article  Google Scholar 

  26. Blouquit, Y., Rhoda, M.-D., Delanoe-Garin, J., Rosa, R., Promé, J.-C., Poyart, C., Puzo, G., Bernassau, J. M., and Rosa, J., 1986, Glycerated hemoglobin, α2 A′282 (EF6) Nε-Glyceryllysine. A new post-translational modification occurring in erythrocyte bisphosphoglyceromutase deficiency. J. Biol. Chem. 261:6758–6764.

    CAS  Google Scholar 

  27. Promé, D., Blouquit, Y., Ponthus, C., Promé, J.-C., and Rosa, J., 1991, Structure of the human adult hemoglobin minor fraction A1b by electrospray and secondary ion mass spectrometry. Pyruvic acid as amino-terminal blocking group, J. Biol. Chem. 266:13050–13054.

    Google Scholar 

  28. Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F., and Whitehouse, C. M., 1989, Electrospray ionization for mass spectrometry of large biomolecules, Science 246:64–71.

    Article  CAS  Google Scholar 

  29. Smith, R. D., Loo, J. A., Edmonds, C. G., Barinaga, C. J., and Udseth, H. R., 1990, New developments in biochemical mass spectrometry: Electrospray ionization. Anal. Chem. 62:882–899.

    Article  CAS  Google Scholar 

  30. De Caterina, M., Esposito, P., Grimaldi, E., Di Maro, G., Scopacasa, F., Ferranti, P., Parlapiano, A., Marlorni, A., Pucci, P., and Marino, G., 1992, Characterization of hemoglobin Lepore variants by advanced mass-spectrometric procedures, Clin. Chem. 38:1444–1448.

    Google Scholar 

  31. Vasseur, C., Blouquit, Y., Kister, J., Promé, D., Kavanaugh, J. S., Rogers, P. H., Guillemin, C., Arnone, A., Galacteros, F., Poyart, C., Rosa, J., and Wajcman, H., 1992, Hemoglobin Thionville. An a-chain variant with a substitution of glutamate for valine at NA-1 and having an acetylated methionine NH2 terminus, J. Biol. Chem. 267:12,682-12,691.

    Google Scholar 

  32. Witkowska, H. E., Lubin, B. H., Beuzard, Y., Baruchel, S., Esseltine, D. W., Vichinsky, E. P., Kleman, K. M., Bardakdjian-Michau, J., Pinkoski, L., Cahn, S., Roitman, E., Green, B. N., Falick, A. M., and Shackleton, C. H. L., 1991, Sickle cell disease in a patient with sickle cell trait and compound heterozygosity for hemoglobin S and hemoglobin Quebec—Chori, N. Engl. J. Med. 325:1150–1154.

    Article  CAS  Google Scholar 

  33. Falick, A. M., Witkowska, H. E., Lubin, B. H., Nagel, R. L., and Shackleton, C. H. L., 1991, Identification of variant hemoglobins by tandem mass spectrometry, in Techniques in Protein Chemistry II (J. J. Villafranca, ed.), Academic Press, San Diego, pp. 557–565.

    Google Scholar 

  34. Ferranti, P., Parlapiano, A., Malorni, A., Pucci, P., Marino, G., Cossu, G., Manca, L., and Masala, B., 1993, Hemoglobin Ozieri: a new a-chain variant [α71 (E20) Ala→Val]. Characterization using FAB-and electrospray-mass spectrometric techniques, Biochem. Biophys. Acta 1162:203–208.

    Article  CAS  Google Scholar 

  35. Covey, T. R., Conboy, J. J., and Henion, J. D., 1989, Collision-induced dissociation of multiply charged peptides, in Proc. 37th Conf. Am. Soc. on Mass Spectrom. and Allied Topics, Miami Beach, FL, May 21–26, 1989, pp. 905-906.

    Google Scholar 

  36. Covey, T. R., Huang, E. C., and Henion, J. D., 1991, Structural characterization of protein tryptic peptides via liquid chromatography/mass spectrometry and collision-induced dissociation of their doubly charged molecular ions, Anal. Chem. 63:1193–1200.

    Article  CAS  Google Scholar 

  37. Witkowska, H. E., Bitsch, F., and Shackleton, C. H. L., 1993, Expediting rare variant hemoglobin characterization by combined HPLC/electrospray mass spectrometry, Hemoglobin, 17:227–242.

    Article  CAS  Google Scholar 

  38. Falick, A. M., Shackleton, C. H. L., Green, B. N., and Witkowska, H. E., 1990, Tandem mass spectrometry in the clinical analysis of variant hemoglobins, Rapid Commun. Mass Spectrom. 4:396–400.

    Article  CAS  Google Scholar 

  39. Jensen, O. N., Höjrup, P., and Roepstorff, P., 1991, Plasma desorption mass spectrometry as a tool in characterization of abnormal proteins. Application to variant human hemoglobins, Anal Biochem. 199:175–183.

    Article  CAS  Google Scholar 

  40. Jensen, O. N., Roepstorff, P., Rozynov, B., Horanyi, M., Szelenyi, J., Hollan, S. R., Aseeva, E. A., and Spivak, V. A., 1991, Plasma desorption mass spectrometry of haemoglobin tryptic peptides for the characterization of a Hungarian a-chain variant, Biol. Mass Spectrom. 20: 579–584.

    Article  CAS  Google Scholar 

  41. Jensen, O. N., and Roepstorff, P., 1991, Application of reversed phase high performance liquid chromatography and plasma desorption mass spectrometry for the characterization of a hemoglobin variant, Hemoglobin 15:497–507.

    Article  CAS  Google Scholar 

  42. Rubin, E. M., Witkowska, H. E., Spangler, E., Curtin, P., Lubin, B. H., Mohandas, N., and Clift, S. M., 1991, Hypoxia-induced in vivo sickling of transgenic mouse red cells, J. Clin. Invest. 87:639–647.

    Article  CAS  Google Scholar 

  43. Imai, K., Fushitani, K., Miyazaki, G., Ishimori, K., Kitagawa, T., Wada, Y., Morimoto, H., Morishima, I., Shih, D. T., and Tame, J., 1991, Site-directed mutagenesis in haemoglobin. Functional role of tyrosine-α42(C7) at the cd-′2 interface, J. Mol. Biol. 218:769–778.

    Article  CAS  Google Scholar 

  44. Ishimori, K., Imai, K., Miyazaki, G., Kitagawa, T., Wada, Y., Morimoto, H., and Morishima, I., 1992, Site-directed mutagenesis in hemoglobin: Functional and structural role of inter-and intrasubunit hydrogen bonds as studied with 37′ and 145′ mutations, Biochemistry 31:3256–3264.

    Article  CAS  Google Scholar 

  45. Coghlan, D., Jones, G., Denton, K. A., Wilson, M. T., Chan, B., Harris, R., Woodrow, J. R., and Ogden, J. E., 1992, Structural and functional characterization of recombinant human haemoglobin A expressed in Saccharomyces cerevisiae, Eur. J. Biochem. 207:931–936.

    Article  CAS  Google Scholar 

  46. Wada, Y., Matsuo, T., and Sakurai, T., 1989, Structural elucidation of hemoglobin variants and other proteins by digit-printing method, Mass Spectrom. Rev. 8:379–434.

    Article  CAS  Google Scholar 

  47. Oliver, R. W. A., and Green, B. N., 1991, The application of electrospray mass spectrometry to the characterization of abnormal or variant haemoglobins, Trends Anal. Chem. 10:85–91.

    Article  CAS  Google Scholar 

  48. Ferrige, A. G., Seddon, M. J., Green, B. N., Jarvis, S. A., and Skilling, J., 1992, Disentangling electrospray spectra with maximum entropy, Rapid Commun. Mass Spectrom. 6:707–711.

    Article  CAS  Google Scholar 

  49. Alter, B. P., Modell, C. B., Fairweather, D., Hobbins, J. C., Mahoney, M. J., Frigoletto, F. D., Sherman, A. S., and Nathan, D. G., 1976, Prenatal diagnosis of hemoglobinopathies. A review of 15 cases, N. Engl. J. Med. 295:1437–1443.

    Article  CAS  Google Scholar 

  50. Larsen, B. S., and McEwen, C. N., 1991, An electrospray ion source for magnetic sector mass spectrometers, J. Am. Soc. Mass Spectrom. 2:205–211.

    Article  CAS  Google Scholar 

  51. Wada, Y., Tamura, J., Musselman, B. D., Kassel, D. B., Sakurai, T., and Matsuo, T., 1992, Electrospray ionization mass spectra of hemoglobin and transferrin by a magnetic sector mass spectrometer. Comparison with theoretical isotopic distributions, Rapid Commun. Mass Spectrom. 6:9–13.

    Article  CAS  Google Scholar 

  52. Loo, J. A., Quinn, J. P., Ryu, S. I., Henry, K. D., Senko, M. W., and McLafferty, F. W., 1992, High-resolution tandem mass spectrometry of large biomolecules, Proc. Natl. Acad. Sci. U.S.A. 89:286–289.

    Article  CAS  Google Scholar 

  53. Huisman, T. H. J., and Wilson, J. B., 1984, The use of HPLC in the study of human hemoglobin variants, Proteides Biol. Fluids 32:1029–1036.

    CAS  Google Scholar 

  54. Wilson, J. B., 1990, Separation of human hemoglobin variants by high performance liquid chromatography, in HPLC of Biological Macromolecules, Methods and Applications (R. Goodieng and F. Regnier, ed.), Marcel Dekker, Inc., New York, pp. 457–472.

    Google Scholar 

  55. Wada, Y., Fujita, T., Hayashi, A., Sakurai, T., and Matsuo, T., 1989, Structural analysis of protein variants by mass spectrometry: Characterization of haemoglobin Providence using a grand-scale mass spectrometer, Biomed. Environ. Mass Spectrom. 18:563–565.

    Article  CAS  Google Scholar 

  56. Abraham, E. G., Reese, A., Stallings, M, and Huisman, T. H. J., 1976/77, Separation of human hemoglobin by DEAE-cellulose chromatography using glycine-KCN-NaCl developers, Hemoglobin 1:27–44.

    Article  Google Scholar 

  57. McDonald, M. J., Shapiro, R., Bleichman, M., Solway, J., and Bunn, H. F., 1978, Glycosylated minor components of human adult hemoglobin. Purification, identification, and partial structural analysis, J. Biol. Chem. 253:2327–2332.

    CAS  Google Scholar 

  58. Righetti, P. G., Gianazza, E., Bianchi-Bosisio, A., and Cossu, G., 1986, Conventional iso-electric focusing and immobilized pH gradients for hemoglobin separation and identification, in The Hemoglobinopathies (T. H. J. Huisman, ed.), Churchill Livingstone, Edinburgh, pp. 47–71.

    Google Scholar 

  59. Rahbar, S., Louis, J., Lee, T., and Asmerom, Y., 1985, Hemoglobin North Chicago (β36[C2]proline→serine): A new high affinity hemoglobin, Hemoglobin 9:559–576.

    Article  CAS  Google Scholar 

  60. Ek, K., Bjellqvist, B., and Righetti, R. G., 1983, Preparative isoelectric focusing in immobilized pH gradients. I. General principles and methodology, J. Biochem. Biophys. Methods 8:135–155.

    Article  CAS  Google Scholar 

  61. Witkowska, E., Bitsch, F., Kleman, K., Pinkoski, L., Kletke, C., Roitman, E., and Shackleton, C., 1992, Integration of ESI MS and LC/ESI MS into the repertoire of techniques used in a hemoglobinopathy laboratory, Proc. Kyoto’ 92 Int. Conf. Biol. Mass Spectrom., (T. Matsuo, ed.), San-ei Publishing Co., Kyoto, Japan, p. 268–269.

    Google Scholar 

  62. Vettore, L., DeMatteis, M. C., Bassetto, M. A., and Pepe, G. M., 1978, Biosynthetic ratio of labelled globin chains in human reticulocytes, determined by electrophoresis on cellulose acetate, Hemoglobin 2:129–141.

    Article  CAS  Google Scholar 

  63. Tegos, C., and Beutler, E., 1980, A simplified method for studies of haemoglobin biosynthesis, Clin. Lab Haemat. 2:191–197.

    CAS  Google Scholar 

  64. Righetti, P. G., Gianazza, E., Gianni, A. M., Comi, P., Giglioni, B., Ottolenghi, S., Secchi, G, and Rossi-Bernardi, L., 1979, Human globin chain separation by isoelectric focusing, J. Biochem. Biophys. Methods 1:45–57.

    Article  CAS  Google Scholar 

  65. Clegg, J. B., Naughton, M. A., and Weatherall, D. J., 1966, Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography and the determination of two new variants, Hb Chesapeake and Hb J (Bangkok), J. Mol. Biol. 19:91–108.

    Article  CAS  Google Scholar 

  66. Pucci, P., Ferranti, P., Marino, G., and Malorni, A., 1989, Characterization of abnormal human haemoglobins by fast atom bombardment mass spectrometry, Biomed. Environ. Mass Spectrom. 18:20–26.

    Article  CAS  Google Scholar 

  67. Huisman, T. H. J., Webber, B., Okonjo, K., Reese, A. L., and Wilson, J. B., 1981, The separation of human hemoglobin chains by high pressure liquid chromatography, in Advances in hemoglobin analysis, (S. M. Hanash and G. J. Brewer, eds.), Alan R. Liss, New York, pp. 23–38.

    Google Scholar 

  68. Congote, L. F., and Kendall, A. G., 1982, Rapid analysis of labeled globin chains without acetone precipitation or dialysis by high-pressure liquid chromatography and ion-exchange chromatography, Anal. Biochem. 123:124–132.

    Article  CAS  Google Scholar 

  69. Shelton, J. B., Shelton, J. R., and Schroeder, W. A., 1984, High performance liquid Chromatographic separation of globin chains on a large-pore C4 column, J. Liquid Chromatog. 7:1969–1977.

    Article  CAS  Google Scholar 

  70. Rahbar, S., and Asmerom, Y., 1989, Rapid HPLC techniques for globin chain synthesis studies, Hemoglobin 13:475–487.

    Article  CAS  Google Scholar 

  71. Katakuse, I., Ichihara, T., Nakabushi, H., Matsuo, T., Matsuda, H., Wada, Y., and Hayashi, A., 1984, Secondary ion mass spectra of tryptic peptides of human hemoglobin chains, Biomed. Mass Spectrom. 11:386–391.

    Article  CAS  Google Scholar 

  72. Schwartz, W. E., Smith, P. K., and Royer, G. P., 1980, N-(β-iodoethytl)trifluoroacetamide: a new reagent for the aminoethylation of thiol groups in proteins, Anal. Biochem. 106:43–48.

    Article  CAS  Google Scholar 

  73. Stone, K. L., LoPresti, M. B., Crawford, J. M., DeAngelis, R., and Williams, K., 1989, Enzymatic digestion of proteins and HPLC peptide isolation, in A Practical Guide to Protein and Peptide Purification for Microsequencing, (P. T. Matsudaira, ed.), Academic Press, San Diego, pp. 33–47.

    Google Scholar 

  74. Kostka, V., and Carpenter, F. H., 1964, Inhibition of chymotryptic activity in crystalline trypsin preparations, J. Biol Chem. 239:1799.

    CAS  Google Scholar 

  75. Stachowiak, K., and Dyckes, D. F., 1989, Peptide mapping using thermospray LC/MS detection: Rapid identification of hemoglobin variants, Peptide Res. 2:214–261.

    Google Scholar 

  76. Craik, C. S., Largman, C., Fletcher, T., Roczniak, S., Barr, P. J., Fletterick, R., and Rutter, W. J., 1985, Redesigning trypsin: Alteration of substrate specificity, Science 228:291–297.

    Article  CAS  Google Scholar 

  77. Lehman, H., and Huntsman, R. G., 1974, Man’s Hemoglobin, North Holland, Amsterdam.

    Google Scholar 

  78. Medzihradszky, K. F., Falick, A. M., Schindler, P. A., and Burlingame, A. L., 1993, Side reactions and non-specific cleavages observed during mass spectrometric analysis of proteins, Anal. Biochem.

    Google Scholar 

  79. Shackleton, C. H. L., Falick, A. M., Green, B. N., and Witkowska, H. E., 1991, Electrospray mass spectrometry in the clinical diagnosis of variant hemoglobins, J. Chromatog. 562:175–190.

    CAS  Google Scholar 

  80. Jekel, P. A., Weijer, W. J., and Beintema, J. J., 1983, Use of endoproteinase Lys-C from Lysobacter enzymogenes in protein sequence analysis, Anal. Biochem. 134:347–354.

    Article  CAS  Google Scholar 

  81. Berezin, I. V., and Martinek, K., 1970, Specificity of a-chymotrypsin, FEBS Lett. 8:261.

    Article  CAS  Google Scholar 

  82. Wada, Y., Ikkala, E., Imai, K., Matsuo, T., Matsuda, H., Lehtinen, M., Hayashi, A., and Lehmann, H., 1987, Structure and function of a new hemoglobin variant, Hb Meilahti (α2β2 36(C2)Pro→Thr), characterized by mass spectrometry, Acto Haemat. 78:109–113.

    Article  CAS  Google Scholar 

  83. Huisman, T. H. J., and Jonxis, J. H. P., 1977, The Hemoglobinopathies: Techniques of Identification, Marcel Dekker, New York.

    Google Scholar 

  84. Houmard, J., and Drapeau, G. R., 1972, Staphylococcal protease: A proteolytic enzyme specific for glutamyl bonds, Proc. Natl. Acad. Sci. U.SA. 69:3506–3509.

    Article  CAS  Google Scholar 

  85. Pucci, P., Ferranti, P., Malorni, A., and Marino, G., 1990, Fast atom bombardment mass spectrometric analysis of haemoglobin variants: Use of V-8 protease in the identification of Hb M Hyde Park and Hb San Jose, Biomed. Environ. Mass Spectrom. 19:568–572.

    Article  CAS  Google Scholar 

  86. Folk, J. E., 1970, Carboxypeptidase B (porcine pancreas), in Proteolytic Enzymes (G. E. Perlmann and L. Lerand, eds.) Methods in Enzymology (S. P. Colowick and N. O. Kaplan, eds.), Vol. XIX, Academic Press, New York, pp. 504–508.

    Chapter  Google Scholar 

  87. De Biasi, R., Spiteri, D., Caldora, M., Iodice, R., Pucci, P., Malorni, A., Ferranti, P., and Marino, G., 1988, Identification by fast atom bombardment mass spectrometry of Hb Indianapolis [β112(G14)Cys→Arg] in a family from Naples, Italy, Hemoglobin 12:323–336.

    Article  Google Scholar 

  88. Hayashi, R., Moore, S., and Stein, W. H., 1973, Carboxypeptidase from yeast, J. Biol. Chem. 248:2296–2302.

    CAS  Google Scholar 

  89. Kuhn, R. W., Walsh, K. A., and Neurath, H., 1974, Isolation and partial characterization of an acid carboxypeptidase from yeast, Biochemistry 13:3871–3877.

    Article  CAS  Google Scholar 

  90. Ryle, A. P., 1970, The porcine pepsin and pepsinogens, in Proteolytic Enzymes (G. E. Perlmann and L. Lerand, eds.) Methods in Enzymology. (S. P. Colowick and N. O. Kaplan, eds.), vol. XIX, Academic Press, New York, p. 316.

    Chapter  Google Scholar 

  91. Casey, R., and Lang, A., 1975, Specific cyanylation and cleavage at cysteine-104 of human haemoglobin a-chain, Biochem. J. 145:251–261.

    CAS  Google Scholar 

  92. Piot, J.-M., Guillochon, D., Zhao, Q., Ricart, G., Fournet, B., and Thomas, D., 1989, Identification of peptides, from a peptic haemoglobin hydrolysate produced by a pilot-plant scale, by high-performance liquid chromatography and mass spectrometry, J. Chromatog. 481:221–231.

    Article  CAS  Google Scholar 

  93. Piot, J. M., Zhao, Q., Guillochon, D., Dhulster, P., Ricart, G., and Thomas, D., 1990, Semi-preparative purification and characterization of peptides from complex haemoglobin hydrolysate by HPLC-mass spectrometry, Chromatographia 30:205–210.

    Article  CAS  Google Scholar 

  94. Witkowski, A., Naggert, J., Witkowska, H. E., Randhawa, Z. I., and Smith, S., 1992, Utilization of an active site serine 101→cysteine mutant to demonstrate the proximity of the catalytic serine 101 and histidine 237 residues in thioesterase II, J. Biol Chem. 267:18,488-18,492.

    Google Scholar 

  95. Jacobsen, G. R., Schaffer, M. H., Stark, G. R., and Vanaman, T. C., 1973, Specific chemical cleavage in high yield at the amino peptide bonds of cysteine and cystine residues, J. Biol. Chem. 248:6583–6591.

    Google Scholar 

  96. Chait, B. T., and Kent, S. B. H., 1992, Weighing naked proteins: practical, high-accuracy mass measurement of peptides and proteins, Science 257:1885–1894.

    Article  CAS  Google Scholar 

  97. Juhasz, P., Papayannopoulos, I. A., Zeng, C., Papov, V., and Biemann, K., 1992, The utility of matrix-assisted laser desorption for the direct analys of enzymatic digests of proteins, Proc. 40th ASMS Conf. Mass Spectrom. Allied Topics, May 31–June 5, 1992, Washington, D.C., pp. 1913-1914.

    Google Scholar 

  98. Hunt, D. F., Alexander, J. E., McCormack, A. L., Martino, P. A., Michel, H., Shabanowitz, J., Sherman, N., Moseley, M. A., Jorgenson, J. W., and Tomer, K. B., 1991, Mass spectrometric methods for protein and peptide sequence analysis, in Techniques in Protein Chemistry II, (J. J. Villafranca, ed.), Academic Press, San Diego, pp. 441–454.

    Google Scholar 

  99. Katta, V., Chowdhury, S. K., and Chait, B. T., 1991, Use of a single-quadrupole mass spectrometer for collision-induced dissociation studies of multiply charged peptide ions produced by electrospray ionization, Anal. Chem. 63:174–178.

    Article  CAS  Google Scholar 

  100. Lee, T. D., and Vemuri, S., 1990, MacProMass: A computer program to correlate mass spectral data to peptide and protein structures, Biomed. Environ. Mass Spectrom. 19:639–645.

    Article  CAS  Google Scholar 

  101. Bitsch, F., Witkowska, H. E., Nugent, K., King, D., and Shackleton, C. H. L., 1992, Assessing structural alterations in natural and recombinant proteins by RP-LC/ESI MS, Proc. 40th ASMS Conf. Mass Spectrom. Allied Topics, May 31–June 5, 1992, Washington, D.C., pp. 428-429.

    Google Scholar 

  102. Henzel, W. J., Bourell, J. H., and Stults, J. T., 1990, Analysis of protein digests by capillary high-performance liquid chromatography and on-line fast atom bombardment mass spectrometry, Anal. Biochem. 187:228–233.

    Article  CAS  Google Scholar 

  103. Davies, M. T., and Lee, T. D., 1992, Analysis of peptide mixtures by capillary high performance liquid chromatography: A practical guide to small-scale separations, Protein Sci. 1:935–944.

    Article  Google Scholar 

  104. Udseth, H. R., Barinaga, C. J., and Smith, R. D., 1990, Developments in combined capillary electrophoresis-ESI-MS., Proc. 38th ASMS Conf. Mass Spectrom. Allied Topics, June 3–8, 1990, Tucson, AZ, pp. 1210-1211.

    Google Scholar 

  105. Ferranti, P., Malorni, A., Pucci, P., Fanali, S., Nardi, A., and Ossicini, L., 1991, Capillary zone electrophoresis and mass spectrometry for the characterization of genetic variants of human hemoglobin, Anal. Biochem. 194:1–8.

    Article  CAS  Google Scholar 

  106. Johansson, I. M., Huang, E. C., Henion, J. D., and Zweigenbaum, J., 1991, Capillary electrophoresis-atmospheric pressure ionization mass spectrometry for the characterization of peptides. Instrumental considerations for mass spectrometric detection, J. Chromatog. 334:311–327.

    Google Scholar 

  107. Wahl, J. H., Goodlett, D. R., Udseth, H. R., and Smith, R. D., 1992, Attomole level capillary electrophoresis-mass spectrometric protein analysis using 5-μm-i. d. capillaries, Anal. Chem. 64:3194–3196.

    Article  CAS  Google Scholar 

  108. Yates III, J. R., Griffin, P. R., Hood, L. E., and Zhou, J. X., 1991, Computer aided interpretation of low energy MS/MS mass spectra of peptides, in Techniques in Protein Chemistry II (J. J. Villafranca, ed.), Academic Press, San Diego, pp. 477–485.

    Google Scholar 

  109. Loo, J. A., Edmonds, C. G., and Smith, R. D., 1990, Primary sequence information from intact proteins by electrospray ionization tandem mass spectrometry, Science 248:201–204.

    Article  CAS  Google Scholar 

  110. Light-Wahl, K. J., Loo, J. A., Edmonds, C. G., Smith, R. D., Witkowska, H. E., Shackleton, C. H. L., and Wu, C.-S. C., 1993, Collisionally activated dissociation and tandem mass spectrometry of intact hemoglobin β-chain variant proteins with electrospray ionization, Biol. Mass Spectrom. 22:112–120.

    Article  CAS  Google Scholar 

  111. Molchanova, T. P., Mirgorodskaya, O. A., Abaturov, L. V., Podtelezhnikov, A. V., Tokarev, Y. N., and Grachev, S. A., 1989, Localization of amino acid substitutions in human hemoglobin. Mass-spectral approximate analysis of tryptic peptides, Molekulyarnaya Biologiya (Russian Original) 23:169–180; English transl. August 1989, Consultants Bureau, New York.

    Google Scholar 

  112. Wada, Y., Matsuo, T., Papayannopoulos, I. A., Costello, C. E., and Biemann, K., 1992, Fast atom bombardment and tandem mass spectrometry for the characterization of hemoglobin variants including a new variant, Int. J. Mass Spectrom. Ion. Processes 122:219–229.

    Article  CAS  Google Scholar 

  113. Lacombe, C., Promé, D., Blouquit, Y., Bardakdjian, J., Arous, N., Mrad, A., Promé, J.-C., and Rosa, J., 1990, New results of hemoglobin variant structure determinations by fast atom bombardment mass spectrometry, Hemoglobin 14:529–548.

    Article  CAS  Google Scholar 

  114. Boissel, J., Kasper, T. J., Shah, S. C., Malone, J. I., and Bunn, H. F., 1985, Amino-terminal processing of proteins: Hemoglobin South Florida, a variant with retention of initiator methionine and Nケ-acetylation, Proc. Natl. Acad. Sci. U.S.A. 82:8448–8452.

    Article  CAS  Google Scholar 

  115. Foldi, J., Horanyi, M., Szelenyi, J. G., Hollan, S. R., Aseeva, E. A., Lutsenko, I. N., Spivak, V. A., Toth, O., Rozynov, B. V., 1989, Hemoglobin Siriraj found in the Hungarian population, Hemoglobin 13:177–180.

    Article  CAS  Google Scholar 

  116. Frigeri, F., Pandolfi, G., Camera, A., Rotoli, B., Ferranti, P., Malorni, A., and Pucci, P., 1990, Hb G-San José: Identification by mass spectrometry, Clin. Chem. Enzym. Commun. 3:289–294.

    Google Scholar 

  117. De Angioletti, M., Maglione, G., Ferranti, P., de Bonis, C., Lacerra, G., Scarallo, A., Pagano, L., Fioretti, G., Cutolo, R., Malorni, A., Pucci, P., and Carestia, C., 1992, Hb City of Hope [β69 (E13) Gly→Ser] in Italy: Association of the gene with haplotype IX, Hemoglobin 16:27–34.

    Article  Google Scholar 

  118. Williamson, D., Nutkins, J., Rosthoj, S., Brennan, S. O., Williams, D. H., and Carrell, R. W., 1990, Characterization of Hb Aalborg, a new unstable hemoglobin variant, by fast atom bombardment mass spectrometry, Hemoglobin 14:137–145.

    Article  CAS  Google Scholar 

  119. Lane, P., Witkowska, H. E., Falick, A. M., Houston, M. L., and McKenna, J. D., 1993, Hemoglobin D-Ibadan-β°thalassemia: Detection by neonatal screening and confirmation by electrospray ionization mass spectrometry, Am. J. Hematol., 44:158–161.

    Article  CAS  Google Scholar 

  120. Marsh, G., Marino, G., Pucci, P., Ferranti, P., Malorni, A., Kaeda, J., Marsh, J., and Luzzatto, L., 1991, A third instance of the high oxygen affinity variant, Hb Heathrow [βl 03 (G5) Phe→Leu]: Identification of the mutation by mass spectrometry and by DNA analysis, Hemoglobin 15:43–51.

    Article  CAS  Google Scholar 

  121. Wada, Y., Hayashi, A., Oka, Y., Matsuo, T., Sakurai, T., Matsuda, H., and Katakuse, I., 1989, Mass spectrometric characterization of a haemoglobin variant, haemoglobin Riyadh, Int. J. Mass Spectrom. Ion Processes 91:34–79.

    Article  Google Scholar 

  122. Wada, Y., Fujita, T., Kidoguchi, K., and Hayashi, Y., 1986, Fetal hemoglobin variants in 80,000 Japanese neonates: high prevalence of Hb F Yamaguchi (Aγ T80 Asp→Asn), Hum. Genet. 72:196–202.

    Article  CAS  Google Scholar 

  123. Fujita, S., Ohta, Y., Saito, S., Kobayashi, Y., Naritomi, Y., Kawaguchi, T., Imamura, T., Wada, Y., and Hayashi, A., 1985, Hemoglobin A2 Honai (α2β290(F6)Glu→Val): A new delta chain variant, Hemoglobin 9:597–607.

    Article  CAS  Google Scholar 

  124. Johnson, R. S., Martin, S. A., and Biemann, K., 1988, Collision-induced fragmentation of [M+H]+ ions of peptides: Side-chain-specific ions, Int. J. Mass Spectrom. Ion Proc. 86:137–154.

    Article  CAS  Google Scholar 

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  1. Children’s Hospital Oakland Research Institute, Oakland, California, 94609, USA

    Cedric H. L. Shackleton & H. Ewa Witkowska

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  1. Cedric H. L. Shackleton
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  1. Departments of Neurology and Biochemistry, and The Charles B. Stout Neuroscience Mass Spectrometry Laboratory, The University of Tennessee, Memphis Memphis, Tennessee, USA

    Dominic M. Desiderio

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Shackleton, C.H.L., Witkowska, H.E. (1994). Mass Spectrometry in the Characterization of Variant Hemoglobins. In: Desiderio, D.M. (eds) Mass Spectrometry. Modern Analytical Chemistry. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1748-5_4

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  • DOI: https://doi.org/10.1007/978-1-4899-1748-5_4

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