Utilization of Hydrogen/Deuterium Exchange in Biopharmaceutical Industry
Authors:
D. Coufalová; B. Vojtěšek; L. Hernychová
Authors‘ workplace:
Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in:
Klin Onkol 2016; 29(Supplementum 4): 59-63
Category:
Review
doi:
https://doi.org/10.14735/amko20164S59
Overview
Background:
The development of biopharmaceutics is the fastest growing segment of the present pharmaceutical industry. The analysis of proteins therapeutics is a challenging task due to their large size and complexity of spatial structure. Any changes in the primary, secondary, tertiary or quaternary protein structure can have huge impact on their function, efficiency and toxicity. Mass spectrometry proved itself to be a powerful tool for analysis of primary protein structure (amino acid sequence) and thanks to the development of new techniques in last years it is able to analyse higher order protein structures. One of these new techniques is hydrogen/deuterium exchange (HDX). HDX is based on exchange of amid protons with deuterium from solution on the protein backbone chain. Protons on the surface of protein are exchanging with deuterium much faster than protons buried inside of protein. HDX results could provide information about spatial protein structure and also about protein-protein interactions and protein-ligand interactions. Furthermore, by analysing of deuterium exchange in different time points this method could give information about dynamic changes of protein structure and dynamics of proteins interactions. Because of possibilities of this method, HDX become attractive method for characterization of protein biopharmaceuticals.
Aims:
This review article is focused on the utilization of mass spectrometry in biopharmaceutical industry and mainly on HDX method and its applications.
Key words:
mass spectrometry – proteomics – protein conformation – drug discovery – drug industry – hydrogen/deuterium exchange
The work was supported by the project MEYS – NPS I – LO1413.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
23. 5. 2016
Accepted:
10. 6. 2016
Sources
1. Kaltashov IA, Eyles SJ. Studies of biomolecular conformations and conformational dynamics by mass spectrometry. Mass Spectrom Rev 2002; 21 (1): 37–71.
2. Dvořáková P, Hernychová L, Vojtěšek B. Analýza proteinů pomocí hmotnostní spektrometrie. Klin Onkol 2014; 27 (Suppl 1): S104–S109. doi: 10.14735/amko2014S104.
3. Zhang Z, Pan H, Chen X. Mass spectrometry for structural characterization of therapeutic antibodies. Mass Spectrom Rev 2009; 28 (1): 147–176. doi: 10.1002/mas. 20190.
4. Srebalus Barnes CA, Lim A. Applications of mass spectrometry for the structural characterization of recombinant protein pharmaceuticals. Mass Spectrom Rev 2007; 26 (3): 370–388.
5. Petoukhov MV, Svergun DI. Analysis of X-ray and neutron scattering from biomacromolecular solutions. Curr Opin Struct Biol 2007; 17 (5): 562–571.
6. Capelle MA, Gurny R, Arvinte T. High throughput screening of protein formulation stability: practical considerations. Eur J Pharm Biopharm 2007; 65 (2): 131–148.
7. Back JW, de Jong L, Muijsers AO et al. Chemical cross-linking and mass spectrometry for protein structural modeling. J Mol Biol 2003; 331 (2): 303–313.
8. Griffith WP, Kaltashov IA. Highly asymmetric interactions between globin chains during hemoglobin assembly revealed by electrospray ionization mass spectrometry. Biochemistry 2003; 42 (33): 10024–10033.
9. Van den Bremer ET, Jiskoot W, James R et al. Probing metal ion binding and conformational properties of the colicin E9 endonuclease by electrospray ionization time-of-flight mass spectrometry. Protein Sci 2002; 11 (7): 1738–1752.
10. Loo JA, Loo RR, Udseth HR et al. Solvent-induced conformational changes of polypeptides probed by electrospray-ionization mass spectrometry. Rapid Commun Mass Spectrom 1991; 5 (3): 101–105.
11. Coufalová D, Vojtěšek B, Hernychová L. Co může přinést studium oligomerizace proteinů v procesu onkogeneze? Klin Onkol 2015; 28 (Suppl 2): 2S6–2S10. doi: 10.14735/amko20152S6.
12. Huang RY, Chen G. Higher order structure characterization of protein therapeutics by hydrogen/deuterium exchange mass spectrometry. Anal Bioanal Chem 2014; 406 (26): 6541–6558. doi: 10.1007/s00216-014-7924-3.
13. Hamuro Y, Coales SJ, Southern MR et al. Rapid analysis of protein structure and dynamics by hydrogen/deuterium exchange mass spectrometry. J Biomol Tech 2003; 14 (3): 171–182.
14. Hvidt A, Nielsen SO. Hydrogen exchange in proteins. Adv Protein Chem 1966; 21: 287–386.
15. Hvidt A, Linderstrom-Lang K. The kinetics of the deuterium exchange of insulin with D2O; an amendment. Biochim Biophys Acta 1955; 16 (1): 168–169.
16. Englander SW, Mayne L. Protein folding studied using hydrogen-exchange labeling and two-dimensional NMR. Annu Rev Biophys Biomol Struct 1992; 21: 243–265.
17. Haris PI, Chapman D. The conformational analysis of peptides using Fourier transform IR spectroscopy. Biopolymers 1995; 37 (4): 251–263.
18. Katta V, Chait BT. Conformational changes in proteins probed by hydrogen-exchange electrospray-ionization mass spectrometry. Rapid Commun Mass Spectrom 1991; 5 (4): 214–217.
19. Chalmers MJ, Busby SA, Pascal BD et al. Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry. Anal Chem 2006; 78 (4): 1005–1014.
20. Kaltashov IA, Bobst CE, Abzalimov RR et al. Conformation and dynamics of biopharmaceuticals: transition of mass spectrometry-based tools from academe to industry. J Am Soc Mass Spectrom 2010; 21 (3): 323–337. doi: 10.1016/j.jasms.2009.10.013.
21. Marciano DP, Dharmarajan V, Griffin PR. HDX-MS guided drug discovery: small molecules and biopharmaceuticals. Curr Opin Struct Biol 2014; 28: 105–111. doi: 10.1016/j.sbi.2014.08.007.
22. Wei H, Mo J, Tao L et al. Hydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications. Drug Discov Today 2014; 19 (1): 95–102. doi: 10.1016/j.drudis.2013.07.019.
23. Beck A, Wagner-Rousset E, Ayoub D et al. Characterization of therapeutic antibodies and related products. Anal Chem 2013; 85 (2): 715–736. doi: 10.1021/ac3032355.
24. Li Pira G, Ivaldi F, Moretti P et al. High throughput T epitope mapping and vaccine development. J Biomed Biotechnol 2010; 2010: 325720. doi: 10.1155/2010/325720.
25. Zhang Q, Willison LN, Tripathi P et al. Epitope mapping of a 95 kDa antigen in complex with antibody by solution-phase amide backbone hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem 2011; 83 (18): 7129–7136. doi: 10.1021/ac201501z.
26. Malito E, Faleri A, Lo Surdo P et al. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen. Proc Natl Acad Sci U S A 2013; 110 (9): 3304–3309. doi: 10.1073/pnas.1222845110.
27. Muthana SM, Campbell CT, Gildersleeve JC. Modifications of glycans: biological significance and therapeutic opportunities. ACS Chem Biol 2012; 7 (1): 31–43. doi: 10.1021/cb2004466.
28. Houde D, Peng Y, Berkowitz SA et al. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Mol Cell Proteomics 2010; 9 (8): 1716–1728. doi: 10.1074/mcp.M900540-MCP200.
29. Pan LY, Salas-Solano O, Valliere-Douglass JF. Conformation and dynamics of interchain cysteine-linked antibody-drug conjugates as revealed by hydrogen/deuterium exchange mass spectrometry. Anal Chem 2014; 86 (5): 2657–2664. doi: 10.1021/ac404003q.
30. Healy AR, Houston DR, Remnant L et al. Discovery of a novel ligand that modulates the protein–protein interactions of the AAA+ superfamily oncoprotein reptin. Chem Sci 2015; 6 (5): 3109–3116. doi: 10.1039/C4SC03885A.
31. Hernychova L, Man P, Verma C et al. Identification of a second Nutlin-3 responsive interaction site in the N-terminal domain of MDM2 using hydrogen/deuterium exchange mass spectrometry. Proteomics 2013; 13 (16): 2512–2525. doi: 10.1002/pmic.201300029.
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