Advanced mass spectrometry-based methods for the analysis of conformational integrity of biopharmaceutical products

Current Pharmaceutical Biotechnology

Volumn 12, Issue 10, 2011, Pages 1517-1529

  Bobst, Cedric E ^a   Kaltashov, Igor A ^a  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

Author keywords

Analytical characterization; Biopharmaceuticals; Charge state distribution; Electrospray ionization; Higher order structure protein; Ion fragmentation hydrogen deuterium exchange; Mass spectrometry; Protein; Protein conformation; Therapeutics

Indexed keywords

GLUCOSYLCERAMIDASE; RECOMBINANT PROTEIN; TRANSFERRIN;

ARTICLE; DEUTERIUM HYDROGEN EXCHANGE; DRUG INDUSTRY; DRUG STRUCTURE; ELECTROSPRAY MASS SPECTROMETRY; ENZYME CONFORMATION; MOLECULAR DYNAMICS; OXIDATION; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN INTERACTION; PROTEIN PROCESSING; PROTEIN STRUCTURE;

EID: 80052358612     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/138920111798357311     Document Type: Article

References (69)

1. Walsh, G. Biopharmaceutical benchmarks 2010. Nat. Biotechnol., 2010, 28, 917-294.
2. Lundblad, R.L. Approaches to the conformational analysis of biopharmaceuticals. Approaches to the Conformational Analysis of Biopharmaceuticals, Ed., Lundblad, R.L. 2010, Boca Raton: CRC Press/Taylor & Francis. p.
3. Kaltashov, I.A.; Eyles, S.J. Studies of biomolecular conformations and conformational dynamics by mass spectrometry. Mass Spectrom. Rev., 2002, 21, 37-71.
4. Zhang, Z.; Pan, H. Chen, X. Mass spectrometry for structural characterization of therapeutic antibodies. Mass Spectrom. Rev., 2009, 28, 147-176.
5. Srebalus-Barnes, C.A.; Lim, A. Applications of mass spectrometry for the structural characterization of recombinant protein pharmaceuticals. Mass Spectrom. Rev., 2007, 26, 370-388.
6. Englander, S.W. Hydrogen exchange and mass spectrometry: A historical perspective. J. Am. Soc. Mass Spectrom., 2006, 17, 1481-1489.
7. Kaltashov, I.A.; Abzalimov, R.R. Do ionic charges in ESI MS provide useful information on macromolecular structure? J. Am. Soc. Mass Spectrom., 2008, 19, 1239-1246.
8. Hernandez, H.; Robinson, C.V. Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry. Nat. Protoc., 2007, 2, 715-726.
9. Yin, S.; Loo, J.A. Mass spectrometry detection and characterization of noncovalent protein complexes. Methods Mol. Biol., 2009, 492, 273-282.
10. Bobst, C.E.; Abzalimov, R.R.; Houde, D.; Kloczewiak, M.; Mhatre, R.; Berkowitz, S.A.; Kaltashov, I.A. Detection and characterization of altered conformations of protein pharmaceuticals using complementary mass spectrometry-based approaches. Anal. Chem., 2008, 80, 7473-7481.
11. Houde, D.; Arndt, J.; Domeier, W.; Berkowitz, S.; Engen, J.R. Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry. Anal. Chem., 2009, 81, 2644-2651.
12. Burkitt, W.; Domann, P.; O'Connor, G. Conformational changes in oxidatively stressed monoclonal antibodies studied by hydrogen exchange mass spectrometry. Protein Sci., 2010, 19, 826-835.
13. Kaltashov, I.A.; Bobst, C.E.; Abzalimov, R.R.; Berkowitz, S.A.; Houde, D. Conformation and dynamics of biopharmaceuticals: transition of mass spectrometry-based tools from academe to industry. J. Am. Soc. Mass Spectrom., 2010, 21, 323-337.
14. Chowdhury, S.K., V. Katta, and B.T. Chait, Probing Conformational Changes in Proteins by Mass Spectrometry. J. Am. Chem. Soc., 1990, 112, 9012-9013.
15. Loo, J.A.; Loo, R.R.; Udseth, H.R.; Edmonds, C.G.; Smith, R.D. Solvent-Induced Conformational Changes of Polypeptides Probed by Electrospray-Ionization Mass Spectrometry. Rapid Commun. Mass Spectrom., 1991, 5, 101-105.
16. Konermann, L.; Douglas, D.J. Equilibrium unfolding of proteins monitored by electrospray ionization mass spectrometry: distinguishing two-state from multi-state transitions. Rapid Commun. Mass Spectrom., 1998, 12, 435-442.
17. Grandori, R. Detecting equilibrium cytochrome c folding intermediates by electrospray ionisation mass spectrometry: Two partially folded forms populate the molten-globule state. Protein Sci., 2002, 11, 453-458.
18. Gumerov, D.R.; Kaltashov, I.A. Dynamics of iron release from transferrin N-lobe studied by electrospray ionization mass spectrometry. Anal. Chem., 2001, 73, 2565-2570.
19. van den Bremer, E.T.; Jiskoot, W.; James, R.; Moore, G.R.; Kleanthous, C.; Heck, A.J.; Maier, C.S. Probing metal ion binding and conformational properties of the colicin E9 endonuclease by electrospray ionization time-of-flight mass spectrometry. Protein Sci., 2002, 11, 1738-1752.
20. Griffith, W.P.; Kaltashov, I.A. Highly asymmetric interactions between globin chains during hemoglobin assembly revealed by electrospray ionization mass spectrometry. Biochemistry, 2003, 42, 10024-10033.
21. Simmons, D.H.; Wilson, D. J.; Lajoie, G.A.; Doherty-Kirby, A.; Konermann, L. Subunit Disassembly and Unfolding Kinetics of Hemoglobin Studied by Time-Resolved Electrospray Mass Spectrometry. Biochemistry, 2004, 43, 14792-14801.
22. Griffith, W.P.; Kaltashov, I.A. Mass spectrometry in the study of hemoglobin: from covalent structure to higher order assembly. Curr. Org. Chem., 2006, 10, 535-553.
23. Dobo, A.; Kaltashov, I.A. Detection of multiple protein conformational ensembles in solution via deconvolution of charge state distributions in ESI MS. Anal. Chem., 2001, 73, 4763-4773.
24. Mohimen, A.; Dobo, A.; Hoerner, J.K.; Kaltashov, I. A. A chemometric approach to detection and characterization of multiple protein conformers in solution using electrospray ionization mass spectrometry. Anal. Chem., 2003, 75, 4139-4147.
25. Kaltashov, I.A.; Mohimen, A. Estimates of protein surface areas in solution by electrospray ionization mass spectrometry. Anal. Chem., 2005, 77, 5370-5379.
26. Bobst, C.E.; Thomas, J.J.; Salinas, P.A.; Savickas,.P; Kaltashov, I. A. Impact of oxidation on protein therapeutics: Conformational dynamics of intact and oxidized acid-β-glucocerebrosidase at nearphysiological pH. Protein Sci., 2010, 19, 2366-2378.
27. Grabowski, G.A. Phenotype, diagnosis, and treatment of Gaucher's disease. Lancet, 2008, 372, 1263-1271.
28. Katta, V.; Chait, B.T. Observation of the Heme Globin Complex in Native Myoglobin by Electrospray-Ionization Mass-Spectrometry. J. Am. Chem. Soc., 1991, 113, 8534-8535.
29. Smith, R.D.; Light-Wahl, J. K.; Winger, E. B.; Loo, A. J. Preservation of noncovalent associations in electrospray ionization mass spectrometry - Multiply charged polypeptide and protein dimers. Org. Mass Spectrom., 1992, 27, 811-821.
30. Kaltashov, I.A.; Zhang, M.; Eyles, S.J.; Abzalimov, R.R. Investigation of structure, dynamics and function of metalloproteins with electrospray ionization mass spectrometry. Anal. Bioanal. Chem., 2006, 386, 472-481.
31. Loo, J.A. Studying noncovalent protein complexes by electrospray ionization mass spectrometry. Mass Spectrom. Rev., 1997, 16, 1-23.
32. Heck, A.J.R. Native mass spectrometry: a bridge between interactomics and structural biology. Nat. Meth., 2008, 5, 927-933.
33. Bruce, J. E. Bio-affinity characterization mass spectrometry. Rapid Commun. Mass Spectrom., 1995, 9, 644-650.
34. Hofstadler, S. A.; K.A. Sannes-Lowery, Applications of ESI-MS in drug discovery: interrogation of noncovalent complexes. Nat. Rev. Drug Discov., 2006, 5, 585-595.
35. Hannah, V.V.; Atmanene, C.; Zeyer, D.; Van Dorsselaer, A.; Sanglier-Cianférani, S. Native MS: an 'ESI' way to support structure- and fragment-based drug discovery. Fut. Med. Chem., 2010, 2, 35-50.
36. Aplin, R.T.; Robinson, V. C.; Schofield, J. C.; Westwood, J. N. Does the observation of noncovalent complexes between biomolecules by electrospray-ionization mass-spectrometry necessarily reflect specific solution interactions. J. Chem. Soc. Chem. Comm., 1994, 1994, 2415-2417.
37. Atmanene, C.; Wagner-Rousset, E.; Malissard, M.; Chol, B.; Robert, A.; Corvaïa, N.; Van Dorsselaer, A.; Beck, A.; Sanglier- Cianférani, S. Extending mass spectrometry contribution to therapeutic monoclonal antibody lead optimization: Characterization of immune complexes using noncovalent ESI-MS. Anal. Chem., 2009, 81, 6364-6373.
38. Leverence, R.; Mason, A.B.; Kaltashov, I.A. Noncanonical interactions between serum transferrin and transferrin receptor evaluated with electrospray ionization mass spectrometry. Proc. Natl. Acad. Sci. USA, 2010, 107, 8123-8128.
39. Singh, M. Transferrin as a targeting ligand for liposomes and anticancer drugs. Curr. Pharm. Des., 1999, 5, 443-451.
40. Qian, Z.M.; Li, H.; Sun, H.; Ho, K. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol. Rev., 2002, 54, 561-87.
41. Daniels, T.R.; Delgado, T.; Helguera, G.; Penichet, M. L. The transferrin receptor part II: Targeted delivery of therapeutic agents into cancer cells. Clin. Immunol., 2006, 121, 159-176.
42. Krishna, M.M.G.; Hoang, L.; Lin, Y.; Englander, S.W. Hydrogen exchange methods to study protein folding. Methods, 2004, 34, 51-64.
43. Bai, Y.; Milne, J.S.; Mayne, L; Englander SW. Primary structure effects on peptide group hydrogen exchange. Proteins, 1993, 17, 75-86.
44. Dempsey, C.E. Hydrogen exchange in peptides and proteins using NMR-spectroscopy. Progr. Nucl. Magn. Res. Spectrosc., 2001, 39, 135-170.
45. Xiao, H.; Hoerner, J.K.; Eyles, S. J.; Dobo, A.; Voigtman, E.; Mel'cuk, A.I.; Kaltashov, I.A. Mapping protein energy landscapes with amide hydrogen exchange and mass spectrometry: I. A generalized model for a two-state protein and comparison with experiment. Protein Sci., 2005, 14, 543-557.
46. Kaltashov, I.A. Probing protein dynamics and function under native and mildly denaturing conditions with hydrogen exchange and mass spectrometry. Int. J. Mass Spectrom., 2005, 240, 249-259.
47. Hoerner, J.K. Xiao, H.; Kaltashov, I.A. Structural and dynamic characteristics of a partially folded state of ubiquitin revealed by hydrogen exchange mass spectrometry. Biochemistry, 2005, 44, 11286-11294.
48. Rosa, J. J.; Richards, F. M. An experimental procedure for increasing the structural resolution of chemical hydrogen-exchange measurements on proteins: application to ribonuclease S peptide. J. Mol. Biol., 1979, 133, 399-416.
49. Englander, J.J.; Rogero, J.R.; S.W. Englander, Protein hydrogen exchange studied by the fragment separation method. Anal. Biochem., 1985, 147, 234-244.
50. Han J. C.; Han G. Y. A procedure for quantitative determination of Tris(2-carboxyethyl)phosphine, an odorless reducing agent more stable and effective than dithiothreitol. Anal. Biochem., 1994, 220, 5-10.
51. Burkitt, W.; Domann, P.; O'Connor, G. Conformational changes in oxidatively stressed monoclonal antibodies studied by hydrogen exchange mass spectrometry. Protein Sci., 2010, 19, 826-35.
52. Houde, D.; Peng, Y.; Berkowitz, S.A.; Engen, J. R. Posttranslational modifications differentially affect IgG1 conformation and receptor binding. Mol. Cel. Proteom., 2010, 9, 1716-1728.
53. Woods, V.L.; Hamuro, Y. Jr. High resolution, high-throughput amide deuterium exchange-mass spectrometry (DXMS) determination of protein binding site structure and dynamics: utility in pharmaceutical design. J. Cell. Biochem., 2001, 37S, 89-98.
54. Stephen, J.C.; Tuske, S.J.; Tomasso, J.C.; Hamuro, Y. Epitope mapping by amide hydrogen/deuterium exchange coupled with immobilization of antibody, on-line proteolysis, liquid chromatography and mass spectrometry. Rapid Commun. Mass Spectrom., 2009, 23, 639-647.
55. Kaltashov, I.A.; Bobst, C.E.; Abzalimov, R.R. H/D exchange and mass spectrometry in the studies of protein conformation and dynamics: Is there a need for a top-down approach? Anal. Chem., 2009, 81, 7892-7899.
56. Del Mar, C.; Greenbaum, E.A.; Mayne, L.; Englander, S.W.; Woods, V.L. Jr. Structure and properties of a-synuclein and other amyloids determined at the amino acid level. Proc. Natl. Acad. Sci. USA, 2005, 102, 15477-15482.
57. Spada, S.; G. Walsh, Directory of approved biopharmaceutical products. 2005, Boca Raton: CRC Press. 317 p.
58. Veronese, F.M.; Mero, A. The impact of PEGylation on biological therapies. BioDrugs, 2008, 22, 315.
59. Abzalimov, R.R.; Kaltashov, I.A. Electrospray ionization mass spectrometry of highly heterogeneous protein systems: protein ion charge state assignment via incomplete charge reduction. Anal. Chem., 2010, 82, 7523-7526.
60. Tropak, M.B.; Kornhaber, G.J.; Rigat, B.A.; Maegawa, G.H.; Buttner, J.D.; Blanchard, J.E.; Murphy, C.; Tuske, S.J.; Coales, S.J.; Hamuro, Y.; Brown, E.D.; Mahuran, D.J. Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/ deuterium exchange mass spectrometry. ChemBioChem, 2008, 9, 2650-2662.
61. Tang, H.Y.; Speicher, D.W. Determination of disulfide-bond linkages in proteins. Curr. Protoc. Protein Sci. 2001, Chapter 11: Unit 11.11.
62. Gau, B.C.; Sharp, J.S.; Rempel, D.L.; Gross, M.L. Fast photochemical oxidation of protein footprints faster than protein unfolding. Anal. Chem., 2009, 81, 6563-6571.
63. Maleknia, S.D.; Ralston, C.Y.; Brenowitz, M.D.; Downard, K.M.; Chance, M.R. Determination of macromolecular folding and structure by synchrotron x- ray radiolysis techniques. Anal Biochem., 2001, 289, 103-115.
64. Konermann, L.; Stocks, B.B.; Pan, Y.; Tong, X. Mass spectrometry combined with oxidative labeling for exploring protein structure and folding. Mass Spectrom. Rev., 2010, 29, 651-667.
65. Mendoza, V. L.; Vachet, R.W. Probing protein structure by amino acid-specific covalent labeling and mass spectrometry. Mass Spectrom. Rev., 2009, 28, 785-815.
66. Back, J.W.; de Jong, L.; Muijsers, A.O.; de Koster, C.G. Chemical cross-linking and mass spectrometry for protein structural modeling. J. Mol. Biol., 2003, 331, 303-313.
67. Robinson, C.V.; Sali, A.; Baumeister, W. The molecular sociology of the cell. Nature, 2007, 450, 973-982.
68. Abzalimov, R.R.; Frimpong, K. A.; Kaltashov, I.A. Gas-phase processes and measurements of macromolecular properties in solution: On the possibility of false positive and false negative signals of protein unfolding. Int. J. Mass Spectrom., 2006, 253, 207-216.
69. Cheng, Y.; Cheng, Y.; Zak, O.; Aisen, P.; Harrison, S.C.; Walz, T. Structure of the human transferrin receptor-transferrin complex. Cell, 2004, 116, 565-576.