Abstract
Background: Biotherapeutics, particularly monoclonal antibodies (mAbs), are a maturing class of drugs capable of treating a wide range of diseases. Therapeutic function and solutionstability are linked to the proper three-dimensional organization of the primary sequence into Higher Order Structure (HOS) as well as the timescales of protein motions (dynamics). Methods that directly monitor protein HOS and dynamics are important for mapping therapeutically relevant protein-protein interactions and assessing properly folded structures. Irreversible covalent protein footprinting Mass Spectrometry (MS) tools, such as site-specific amino acid labeling and hydroxyl radical footprinting are analytical techniques capable of monitoring the side chain solvent accessibility influenced by tertiary and quaternary structure. Here we discuss the methodology, examples of biotherapeutic applications, and the future directions of irreversible covalent protein footprinting MS in biotherapeutic research and development.
Conclusion: Bottom-up mass spectrometry using irreversible labeling techniques provide valuable information for characterizing solution-phase protein structure. Examples range from epitope mapping and protein-ligand interactions, to probing challenging structures of membrane proteins. By paring these techniques with hydrogen-deuterium exchange, spectroscopic analysis, or static-phase structural data such as crystallography or electron microscopy, a comprehensive understanding of protein structure can be obtained.
Keywords: Structural mass spectrometry, protein footprinting, biotherapeutics, higher order structure, hydroxyl radical footprinting, covalent labeling.
Graphical Abstract
[1]
Ecker, D.M.; Jones, S.D.; Levine, H.L. The therapeutic monoclonal antibody market. MAbs, 2015, 7(1), 9-14.
[3]
Leader, B.; Baca, Q.J.; Golan, D.E. Protein therapeutics: A summary and pharmacological classification. Nat. Rev. Drug Discov., 2008, 7(1), 21-39.
[6]
Jefferis, R. Antibody therapeutics: Isotype and glycoform selection. Expert Opin. Biol. Ther., 2007, 7(9), 1401-1413.
[7]
Jefferis, R. Isotype and glycoform selection for antibody therapeutics. Arch. Biochem. Biophys., 2012, 526(2), 159-166.
[8]
Krawczyk, K.; Dunbar, J.; Deane, C.M. Computational tools for aiding rational antibody design. Methods Mol. Biol., 2017, 1529, 399-416.
[9]
Bostrom, J.; Lee, C.V.; Haber, L.; Fuh, G. Improving antibody binding affinity and specificity for therapeutic development. Methods Mol. Biol., 2009, 525, 353-376.
[10]
Weiner, G.J. Building better monoclonal antibody-based therapeutics. Nat. Rev. Cancer, 2015, 15(6), 361-370.
[11]
Irani, V.; Guy, A.J.; Andrew, D.; Beeson, J.G.; Ramsland, P.A.; Richards, J.S. Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases. Mol. Immunol., 2015, 67(2 Pt A), 171-182.
[12]
Stanfield, R.L.; Takimoto-Kamimura, M.; Rini, J.M.; Profy, A.T.; Wilson, I.A. Major antigen-induced domain rearrangements in an antibody. Structure, 1993, 1(2), 83-93.
[13]
Gershoni, J.M.; Roitburd-Berman, A.; Siman-Tov, D.D.; Tarnovitski Freund, N.; Weiss, Y. Epitope mapping: The first step in developing epitope-based vaccines. BioDrugs, 2007, 21(3), 145-156.
[14]
Wang, W.; Ye, W.; Yu, Q.; Jiang, C.; Zhang, J.; Luo, R.; Chen, H.F. Conformational selection and induced fit in specific antibody and antigen recognition: SPE7 as a case study. J. Phys. Chem. B, 2013, 117(17), 4912-4923.
[15]
Bongini, L.; Fanelli, D.; Piazza, F.; De Los Rios, P.; Sandin, S.; Skoglund, U. Freezing immunoglobulins to see them move. Proc. Natl. Acad. Sci. USA, 2004, 101(17), 6466-6471.
[16]
Sandin, S.; Ofverstedt, L.G.; Wikstrom, A.C.; Wrange, O.; Skoglund, U. Structure and flexibility of individual immunoglobulin G molecules in solution. Structure, 2004, 12(3), 409-415.
[17]
Saphire, E.O.; Stanfield, R.L.; Crispin, M.D.; Parren, P.W.; Rudd, P.M.; Dwek, R.A.; Burton, D.R.; Wilson, I.A. Contrasting IgG structures reveal extreme asymmetry and flexibility. J. Mol. Biol., 2002, 319(1), 9-18.
[18]
Bongini, L.; Fanelli, D.; Piazza, F.; De Los Rios, P.; Sandin, S.; Skoglund, U. Dynamics of antibodies from cryo-electron tomography. Biophys. Chem., 2005, 115(2-3), 235-240.
[19]
Henzler-Wildman, K.; Kern, D. Dynamic personalities of proteins. Nature, 2007, 450(7172), 964-972.
[20]
Correia, I.; Sung, J.; Burton, R.; Jakob, C.G.; Carragher, B.; Ghayur, T.; Radziejewski, C. The structure of dual-variable-domain immunoglobulin molecules alone and bound to antigen. MAbs, 2013, 5(3), 364-372.
[21]
Zhang, X.; Zhang, L.; Tong, H.; Peng, B.; Rames, M.J.; Zhang, S.; Ren, G. 3D structural fluctuation of IgG1 antibody revealed by individual particle electron tomography. Sci. Rep., 2015, 5, 9803.
[22]
Zhang, H.M.; Li, C.; Lei, M.; Lundin, V.; Lee, H.Y.; Ninonuevo, M.; Lin, K.; Han, G.; Sandoval, W.; Lei, D.; Ren, G.; Zhang, J.; Liu, H. Structural and functional characterization of a hole-hole homodimer variant in a “Knob-Into-Hole” bispecific antibody. Anal. Chem., 2017, 89(24), 13494-13501.
[23]
Harris, L.J.; Larson, S.B.; Hasel, K.W.; McPherson, A. Refined structure of an intact IgG2a monoclonal antibody. Biochemistry, 1997, 36(7), 1581-1597.
[24]
Harris, L.J.; Skaletsky, E.; McPherson, A. Crystallographic structure of an intact IgG1 monoclonal antibody. J. Mol. Biol., 1998, 275(5), 861-872.
[25]
Saphire, E.O.; Parren, P.W.; Pantophlet, R.; Zwick, M.B.; Morris, G.M.; Rudd, P.M.; Dwek, R.A.; Stanfield, R.L.; Burton, D.R.; Wilson, I.A. Crystal structure of a neutralizing human IGG against HIV-1: A template for vaccine design. Science, 2001, 293(5532), 1155-1159.
[26]
Dunbar, J.; Krawczyk, K.; Leem, J.; Baker, T.; Fuchs, A.; Georges, G.; Shi, J.; Deane, C.M. SAbDab: The structural antibody database. Nucleic Acids Res., 2014, 42(D1), D1140-D1146.
[27]
Sung, J.J.; Pardeshi, N.N.; Mulder, A.M.; Mulligan, S.K.; Quispe, J.; On, K.; Carragher, B.; Potter, C.S.; Carpenter, J.F.; Schneemann, A. Transmission electron microscopy as an orthogonal method to characterize protein aggregates. J. Pharm. Sci., 2015, 104(2), 750-759.
[28]
Krissinel, E.; Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol., 2007, 372(3), 774-797.
[29]
Plath, F.; Ringler, P.; Graff-Meyer, A.; Stahlberg, H.; Lauer, M.E.; Rufer, A.C.; Graewert, M.A.; Svergun, D.; Gellermann, G.; Finkler, C.; Stracke, J.O.; Koulov, A.; Schnaible, V. Characterization of mAb dimers reveals predominant dimer forms common in therapeutic mAbs. MAbs, 2016, 8(5), 928-940.
[30]
Lapelosa, M.; Patapoff, T.W.; Zarraga, I.E. Molecular simulations of the pairwise interaction of monoclonal antibodies. J. Phys. Chem. B, 2014, 118(46), 13132-13141.
[31]
De Vivo, M.; Masetti, M.; Bottegoni, G.; Cavalli, A. Role of molecular dynamics and related methods in drug discovery. J. Med. Chem., 2016, 59(9), 4035-4061.
[32]
Soler, M.A.; de Marco, A.; Fortuna, S. Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies. Sci. Rep., 2016, 6, 34869.
[33]
Paul, R.; Graff-Meyer, A.; Stahlberg, H.; Lauer, M.E.; Rufer, A.C.; Beck, H.; Briguet, A.; Schnaible, V.; Buckel, T.; Boeckle, S. Structure and function of purified monoclonal antibody dimers induced by different stress conditions. Pharm. Res., 2012, 29(8), 2047-2059.
[34]
Brandt, J.P.; Patapoff, T.W.; Aragon, S.R. Construction, MD simulation, and hydrodynamic validation of an all-atom model of a monoclonal IgG antibody. Biophys. J., 2010, 99(3), 905-913.
[35]
Lin, J.C.; Glover, Z.K.; Sreedhara, A. Assessing the utility of circular dichroism and FTIR spectroscopy in monoclonal-antibody comparability studies. J. Pharm. Sci., 2015, 104(12), 4459-4466.
[36]
Razinkov, V.I.; Treuheit, M.J.; Becker, G.W. Methods of high throughput biophysical characterization in biopharmaceutical development. Curr. Drug Discov. Technol., 2013, 10(1), 59-70.
[37]
Benevides, J.M.; Overman, S.A.; Thomas, G.J. Jr. Raman spectroscopy
of proteins. Curr. Protoc. Protein Sci , 2004. Chap. 17, unit
17.8.
[38]
Ma, L.; Yang, F.; Zheng, J. Application of fluorescence resonance energy transfer in protein studies. J. Mol. Struct., 2014, 1077, 87-100.
[39]
Goulet, D.R.; Orcutt, S.J.; Zwolak, A.; Rispens, T.; Labrijn, A.F.; de Jong, R.N.; Atkins, W.M.; Chiu, M.L. Kinetic mechanism of controlled Fab-arm exchange for the formation of bispecific immunoglobulin G1 antibodies. J. Biol. Chem., 2018, 293(2), 651-661.
[40]
Rispens, T.; Davies, A.M.; Ooijevaar-de Heer, P.; Absalah, S.; Bende, O.; Sutton, B.J.; Vidarsson, G.; Aalberse, R.C. Dynamics of inter-heavy chain interactions in human immunoglobulin G (IgG) subclasses studied by kinetic Fab arm exchange. J. Biol. Chem., 2014, 289(9), 6098-6109.
[41]
Pervushin, K.; Riek, R.; Wider, G.; Wuthrich, K. Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. Proc. Natl. Acad. Sci. USA, 1997, 94(23), 12366-12371.
[42]
Fiaux, J.; Bertelsen, E.B.; Horwich, A.L.; Wuthrich, K. NMR analysis of a 900K GroEL GroES complex. Nature, 2002, 418, 207-211.
[43]
Arbogast, L.W.; Brinson, R.G.; Formolo, T.; Hoopes, J.T.; Marino, J.P., II (1)H(N), (15)N Correlated NMR methods at natural abundance for obtaining structural maps and statistical comparability of monoclonal antibodies. Pharm. Res., 2016, 33(2), 462-475.
[44]
Arbogast, L.W.; Brinson, R.G.; Marino, J.P. Mapping monoclonal antibody structure by 2D 13C NMR at natural abundance. Anal. Chem., 2015, 87(7), 3556-3561.
[45]
Eschweiler, J.D.; Kerr, R.; Rabuck-Gibbons, J.; Ruotolo, B.T. Sizing up protein-ligand complexes: The rise of structural mass spectrometry approaches in the pharmaceutical sciences. Annu. Rev. Anal. Chem. (Palo Alto, Calif.), 2017, 10(1), 25-44.
[46]
Zhang, Y.; Cui, W.; Wecksler, A.T.; Zhang, H.; Molina, P.; Deperalta, G.; Gross, M.L. Native MS and ECD characterization of a fab-antigen complex may facilitate crystallization for X-ray diffraction. J. Am. Soc. Mass Spectrom., 2016, 27(7), 1139-1142.
[47]
Haberger, M.; Leiss, M.; Heidenreich, A.K.; Pester, O.; Hafenmair, G.; Hook, M.; Bonnington, L.; Wegele, H.; Haindl, M.; Reusch, D.; Bulau, P. Rapid characterization of biotherapeutic proteins by size-exclusion chromatography coupled to native mass spectrometry. MAbs, 2016, 8(2), 331-339.
[48]
Ferguson, C.N.; Gucinski-Ruth, A.C. Evaluation of ion mobility-mass spectrometry for comparative analysis of monoclonal antibodies. J. Am. Soc. Mass Spectrom., 2016, 27(5), 822-833.
[49]
Zhang, Z.; Smith, D.L. Determination of amide hydrogen exchange by mass spectrometry: A new tool for protein structure elucidation. Protein Sci., 1993, 2(4), 522-531.
[50]
Englander, S.W. Hydrogen exchange and mass spectrometry: A historical perspective. J. Am. Soc. Mass Spectrom., 2006, 17(11), 1481-1489.
[51]
Maleknia, S.D.; Brenowitz, M.; Chance, M.R. Millisecond radiolytic modification of peptides by synchrotron X-rays identified by mass spectrometry. Anal. Chem., 1999, 71(18), 3965-3973.
[52]
Xu, G.H.; Chance, M.R. Hydroxyl radical-mediated modification of proteins as probes for structural proteomics. Chem. Rev., 2007, 107, 3514-3543.
[53]
Zhang, H.; Wen, J.; Huang, R.Y.; Blankenship, R.E.; Gross, M.L. Mass spectrometry-based carboxyl footprinting of proteins: Method evaluation. Int. J. Mass Spectrom., 2012, 312, 78-86.
[54]
Zhang, Y.; Fonslow, B.R.; Shan, B.; Baek, M.C.; Yates, J.R., III Protein analysis by shotgun/bottom-up proteomics. Chem. Rev., 2013, 113, 2343-2394.
[55]
Zhang, Z.; Pan, H.; Chen, X. Mass spectrometry for structural characterization of therapeutic antibodies. Mass Spectrom. Rev., 2009, 28(1), 147-176.
[56]
Mo, J.; Tymiak, A.A.; Chen, G. Structural mass spectrometry in biologics discovery: Advances and future trends. Drug Discov. Today, 2012, 17(23-24), 1323-1330.
[57]
Chalmers, M.J.; Busby, S.A.; Pascal, B.D.; He, Y.; Hendrickson, C.L.; Marshall, A.G.; Griffin, P.R. Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry. Anal. Chem., 2006, 78(4), 1005-1014.
[58]
Wales, T.E.; Fadgen, K.E.; Gerhardt, G.C.; Engen, J.R. High-speed and high-resolution UPLC separation at zero degrees Celsius. Anal. Chem., 2008, 80(17), 6815-6820.
[59]
Balasubramanian, B.; Pogozelski, W.K.; Tullius, T.D. DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. Proc. Natl. Acad. Sci. USA, 1998, 95(17), 9738-9743.
[60]
Galas, D.J.; Schmitz, A. DNAse footprinting: A simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res., 1978, 5(9), 3157-3170.
[61]
Sclavi, B.; Woodson, S.; Sullivan, M.; Chance, M.R.; Brenowitz, M. Time-resolved synchrotron X-ray “footprinting”, a new approach to the study of nucleic acid structure and function: application to protein-DNA interactions and RNA folding. J. Mol. Biol., 1997, 266(1), 144-159.
[62]
Aydogan, B.; Marshall, D.T.; Swarts, S.G.; Turner, J.E.; Boone, A.J.; Richards, N.G.; Bolch, W.E. Site-specific OH attack to the sugar moiety of DNA: A comparison of experimental data and computational simulation. Radiat. Res., 2002, 157(1), 38-44.
[63]
Kent, O.; Chaulk, S.G.; MacMillan, A.M. Kinetic analysis of the M1 RNA folding pathway. J. Mol. Biol., 2000, 304(5), 699-705.
[64]
Ralston, C.Y.; He, Q.; Brenowitz, M.; Chance, M.R. Stability and cooperativity of individual tertiary contacts in RNA revealed through chemical denaturation. Nat. Struct. Biol., 2000, 7(5), 371-374.
[65]
Ralston, C.Y.; Sclavi, B.; Sullivan, M.; Deras, M.L.; Woodson, S.A.; Chance, M.R.; Brenowitz, M. Time-resolved synchrotron X-ray footprinting and its application to RNA folding. Methods Enzymol., 2000, 317, 353-368.
[66]
Brenowitz, M.; Chance, M.R.; Dhavan, G.; Takamoto, K. Probing the structural dynamics of nucleic acids by quantitative time-resolved and equilibrium hydroxyl radical “footprinting”. Curr. Opin. Struct. Biol., 2002, 12(5), 648-653.
[67]
Adilakshmi, T.; Bellur, D.L.; Woodson, S.A. Concurrent nucleation of 16S folding and induced fit in 30S ribosome assembly. Nature, 2008, 455(7217), 1268-1272.
[68]
Kiselar, J.G.; Maleknia, S.D.; Sullivan, M.; Downard, K.M.; Chance, M.R. Hydroxyl radical probe of protein surfaces using synchrotron X-ray radiolysis and mass spectrometry. Int. J. Radiat. Biol., 2002, 78(2), 101-114.
[69]
Xu, G.; Chance, M.R. Radiolytic modification of acidic amino acid residues in peptides: probes for examining protein-protein interactions. Anal. Chem., 2004, 76(5), 1213-1221.
[70]
Hambly, D.M.; Gross, M.L. Laser flash photolysis of hydrogen peroxide to oxidize protein solvent-accessible residues on the microsecond timescale. J. Am. Soc. Mass Spectrom., 2005, 16(12), 2057-2063.
[71]
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(16), 6563-6571.
[72]
Konermann, L.; Vahidi, S.; Sowole, M.A. Mass spectrometry methods for studying structure and dynamics of biological macromolecules. Anal. Chem., 2014, 86(1), 213-232.
[73]
Wang, L.; Chance, M.R. Protein footprinting comes of age: Mass spectrometry for biophysical structure assessment. Mol. Cell. Proteomics, 2017, 16(5), 706-716.
[74]
Aye, T.T.; Low, T.Y.; Sze, S.K. Nanosecond laser-induced photochemical oxidation method for protein surface mapping with mass spectrometry. Anal. Chem., 2005, 77(18), 5814-5822.
[75]
Sharp, J.S.; Tomer, K.B. Analysis of the oxidative damage-induced conformational changes of apo- and holocalmodulin by dose-dependent protein oxidative surface mapping. Biophys. J., 2007, 92(5), 1682-1692.
[76]
Hambly, D.; Gross, M. Laser flash photochemical oxidation to locate heme binding and conformational changes in myoglobin. Int. J. Mass Spectrom., 2007, 259, 124-129.
[77]
Kaur, P.; Tomechko, S.; Kiselar, J.; Shi, W.; Deperalta, G.; Wecksler, A.T.; Gokulrangan, G.; Ling, V.; Chance, M.R. Characterizing monoclonal antibody structure by carbodiimide/GEE footprinting. MAbs, 2014, 6(6), 1486-1499.
[78]
Mendoza, V.L.; Vachet, R.W. Probing protein structure by amino acid-specific covalent labeling and mass spectrometry. Mass Spectrom. Rev., 2009, 28(5), 785-815.
[79]
Xu, G.; Kiselar, J.; He, Q.; Chance, M.R. Secondary reactions and strategies to improve quantitative protein footprinting. Anal. Chem., 2005, 77(10), 3029-3037.
[80]
Chance, M.R.; Sclavi, B.; Woodson, S.A.; Brenowitz, M. Examining the conformational dynamics of macromolecules with time-resolved synchrotron X-ray ‘footprinting’. Structure, 1997, 5(7), 865-869.
[81]
Woodson, S.A.; Deras, M.L.; Brenowitz, M. Time-resolved hydroxyl radical footprinting of RNA with X-rays; , 2001.
[82]
Zhang, Y.; Rempel, D.L.; Zhang, H.; Gross, M.L. An improved Fast Photochemical Oxidation of Proteins (FPOP) platform for protein therapeutics. J. Am. Soc. Mass Spectrom., 2015, 26(3), 526-529.
[83]
Niu, B.; Zhang, H.; Giblin, D.; Rempel, D.L.; Gross, M.L. Dosimetry determines the initial OH radical concentration in Fast Photochemical Oxidation of Proteins (FPOP). J. Am. Soc. Mass Spectrom., 2015, 26(5), 843-846.
[84]
Vahidi, S.; Konermann, L. Probing the time scale of FPOP (Fast Photochemical Oxidation of Proteins): Radical reactions extend over tens of milliseconds. J. Am. Soc. Mass Spectrom., 2016, 27(7), 1156-1164.
[85]
Kaur, P.; Kiselar, J.G.; Chance, M.R. Integrated algorithms for high-throughput examination of covalently labeled biomolecules by structural mass spectrometry. Anal. Chem., 2009, 81(19), 8141-8149.
[86]
Charvatova, O.; Foley, B.L.; Bern, M.W.; Sharp, J.S.; Orlando, R.; Woods, R.J. Quantifying protein interface footprinting by hydroxyl radical oxidation and molecular dynamics simulation: Application to galectin-1. J. Am. Soc. Mass Spectrom., 2008, 19(11), 1692-1705.
[88]
Rey, M.; Sarpe, V.; Burns, K.M.; Buse, J.; Baker, C.A.; van Dijk, M.; Wordeman, L.; Bonvin, A.M.; Schriemer, D.C. Mass spec studio for integrative structural biology. Structure, 2014, 22(10), 1538-1548.
[89]
Rinas, A.; Espino, J.A.; Jones, L.M. An efficient quantitation strategy for hydroxyl radical-mediated protein footprinting using Proteome Discoverer. Anal. Bioanal. Chem., 2016, 408(11), 3021-3031.
[90]
Jones, L.M. J, B.S.; J, A.C.; Gross, M.L. Fast photochemical oxidation of proteins for epitope mapping. Anal. Chem., 2011, 83(20), 7657-7661.
[91]
Tong, X.; Wren, J.C.; Konermann, L. Effects of protein concentration on the extent of gamma-ray-mediated oxidative labeling studied by electrospray mass spectrometry. Anal. Chem., 2007, 79(16), 6376-6382.
[92]
Gupta, S.; Sullivan, M.; Toomey, J.; Kiselar, J.; Chance, M.R. The beamline X28C of the center for synchrotron biosciences: A national resource for biomolecular structure and dynamics experiments using synchrotron footprinting. J. Synchrotron Radiat., 2007, 14(Pt 3), 233-243.
[93]
Xie, B.; Sharp, J. Hydroxyl radical dosimetry for high flux hydroxyl radical protein footprinting applications using a simple optical detection method. Anal. Chem., 2015, 87(21), 10719-10723.
[94]
Guttman, M.; Garcia, N.K.; Cupo, A.; Matsui, T.; Julien, J.P.; Sanders, R.W.; Wilson, I.A.; Moore, J.P.; Lee, K.K. CD4-induced activation in a soluble HIV-1 Env trimer. Structure, 2014, 22(7), 974-984.
[95]
Niu, B.; Mackness, B.C.; Rempel, D.L.; Zhang, H.; Cui, W.; Matthews, C.R.; Zitzewitz, J.A.; Gross, M.L. Incorporation of a reporter peptide in FPOP compensates for adventitious scavengers and permits time-dependent measurements. J. Am. Soc. Mass Spectrom., 2017, 28(2), 389-392.
[97]
Huang, W.; Ravikumar, K.M.; Chance, M.R.; Yang, S.C. Quantitative mapping of protein structure by hydroxyl radical footprinting mediated structural mass spectrometry: A protection factor analysis. Biophys. J., 2015, 108(1), 107-115.
[98]
Kamal, J.K.A.; Chance, M.R. Modeling of protein binary complexes using structural mass spectrometry data. Protein Sci., 2008, 17(1), 79-94.
[99]
Pan, L.Y.; Salas-Solano, O.; Valliere-Douglass, J.F. Antibody structural integrity of site-specific antibody-drug conjugates investigated by hydrogen/deuterium exchange mass spectrometry. Anal. Chem., 2015, 87(11), 5669-5676.
[100]
Pan, L.Y.; Salas-Solano, O.; Valliere-Douglass, J.F. 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.
[101]
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(7), 2644-2651.
[102]
Houde, D.; Peng, Y.; Berkowitz, S.A.; Engen, J.R. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Mol. Cell. Proteomics, 2010, 9(8), 1716-1728.
[103]
Lei, M.; Kao, Y.H.; Schoneich, C. Using lysine-reactive fluorescent dye for surface characterization of a mAb. J. Pharm. Sci., 2015, 104(3), 995-1004.
[105]
Gresl, T.; Storz, U.; Sandercock, C. An update on obtaining and enforcing therapeutic antibody patent claims. Nat. Biotechnol., 2016, 34(12), 1242-1245.
[106]
Baerga-Ortiz, A.; Hughes, C.A.; Mandell, J.G.; Komives, E.A. Epitope mapping of a monoclonal antibody against human thrombin by H/D-exchange mass spectrometry reveals selection of a diverse sequence in a highly conserved protein. Protein Sci., 2002, 11(6), 1300-1308.
[107]
Wecksler, A.T.; Kalo, M.S.; Deperalta, G. Mapping of Fab-1:VEGF interface using carboxyl group footprinting mass spectrometry. J. Am. Soc. Mass Spectrom., 2015, 26(12), 2077-2080.
[108]
Zhang, Y.; Wecksler, A.T.; Molina, P.; Deperalta, G.; Gross, M.L. Mapping the binding interface of VEGF and a monoclonal antibody Fab-1 fragment with Fast Photochemical Oxidation of Proteins (FPOP) and mass spectrometry. J. Am. Soc. Mass Spectrom., 2017, 28(5), 850-858.
[109]
Li, J.; Wei, H.; Krystek, S.R.; Bond, D.; Brender, T.M.; Cohen, D.; Feiner, J.; Hamacher, N.; Harshman, J.; Huang, R.Y.C.; Julien, S.H.; Lin, Z.; Moore, K.; Mueller, L.; Noriega, C.; Sejwal, P.; Sheppard, P.; Stevens, B.; Chen, G.D.; Tyrniak, A.A.; Gross, M.L.; Schneeweis, L.A. Mapping the energetic epitope of an Antibody/Interleukin-23 interaction with hydrogen/deuterium exchange, fast photochemical oxidation of proteins mass spectrometry, and alanine shave mutagenesis. Anal. Chem., 2017, 89(4), 2250-2258.
[110]
Li, X.Y.; Li, Z.X.; Xie, B.; Sharp, J.S. Improved identification and relative quantification of sites of peptide and protein oxidation for hydroxyl radical footprinting. J. Am. Soc. Mass Spectrom., 2013, 24(11), 1767-1776.
[111]
Wang, L.; Qin, Y.; Ilchenko, S.; Bohon, J.; Shi, W.; Cho, M.W.; Takamoto, K.; Chance, M.R. Structural analysis of a highly glycosylated and unliganded gp120-based antigen using mass spectrometry. Biochemistry, 2010, 49(42), 9032-9045.
[112]
Li, X.; Grant, O.C.; Ito, K.; Wallace, A.; Wang, S.; Zhao, P.; Wells, L.; Lu, S.; Woods, R.J.; Sharp, J.S. Structural analysis of the glycosylated intact HIV-1 gp120-b12 antibody complex using hydroxyl radical protein footprinting. Biochemistry, 2017, 56(7), 957-970.
[113]
Guttman, M.; Cupo, A.; Julien, J.P.; Sanders, R.W.; Wilson, I.A.; Moore, J.P.; Lee, K.K. Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env. Nat. Commun., 2015, 6, 6144.
[114]
Harris, R.J.; Shire, S.J.; Winter, C. Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodies. Drug Dev. Res., 2004, 61(3), 137-154.
[115]
Beck, A.; Wagner-Rousset, E.; Ayoub, D.; Van Dorsselaer, A.; Sanglier-Cianferani, S. Characterization of therapeutic antibodies and related products. Anal. Chem., 2013, 85(2), 715-736.
[116]
Liu, H.C.; Gaza-Bulseco, G.; Faldu, D.; Chumsae, C.; Sun, J. Heterogeneity of monoclonal antibodies. J. Pharm. Sci., 2008, 97(7), 2426-2447.
[117]
Liu, H.C.; Nowak, C.; Shao, M.; Ponniah, G.; Neill, A. Impact of cell culture on recombinant monoclonal antibody product heterogeneity. Biotechnol. Prog., 2016, 32(5), 1103-1112.
[118]
Manning, M.C.; Chou, D.K.; Murphy, B.M.; Payne, R.W.; Katayama, D.S. Stability of protein pharmaceuticals: An update. Pharm. Res., 2010, 27(4), 544-575.
[119]
Majumdar, R.; Manikwar, P.; Hickey, J.M.; Samra, H.S.; Sathish, H.A.; Bishop, S.M.; Middaugh, C.R.; Volkin, D.B.; Weis, D.D. Effects of salts from the hofmeister series on the conformational stability, aggregation propensity, and local flexibility of an IgG1 monoclonal antibody. Biochemistry, 2013, 52(19), 3376-3389.
[120]
Manikwar, P.; Majumdar, R.; Hickey, J.M.; Thakkar, S.V.; Samra, H.S.; Sathish, H.A.; Bishop, S.M.; Middaugh, C.R.; Weis, D.D.; Volkin, D.B. Correlating excipient effects on conformational and storage stability of an IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry. J. Pharm. Sci., 2013, 102(7), 2136-2151.
[121]
Majumdar, R.; Middaugh, C.R.; Weis, D.D.; Volkin, D.B. Hydrogen-deuterium exchange mass spectrometry as an emerging analytical tool for stabilization and formulation development of therapeutic monoclonal antibodies. J. Pharm. Sci., 2015, 104(2), 327-345.
[122]
Arora, J.; Hickey, J.M.; Majumdar, R.; Esfandiary, R.; Bishop, S.M.; Samra, H.S.; Middaugh, C.R.; Weis, D.D.; Volkin, D.B. Hydrogen exchange mass spectrometry reveals protein interfaces and distant dynamic coupling effects during the reversible self-association of an IgG1 monoclonal antibody. MAbs, 2015, 7(3), 525-539.
[123]
Arora, J.; Hu, Y.; Esfandiary, R.; Sathish, H.A.; Bishop, S.M.; Joshi, S.B.; Middaugh, C.R.; Volkin, D.B.; Weis, D.D. Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self-association, cluster formation, and elevated viscosity. MAbs, 2016, 8(8), 1561-1574.
[124]
Moussa, E.M.; Singh, S.K.; Kimmel, M.; Nema, S.; Topp, E.M. Probing the conformation of an IgG1 monoclonal antibody in lyophilized solids using solid-state Hydrogen-Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS). Mol. Pharm., 2018, 15(2), 356-368.
[125]
Moussa, E.M.; Wilson, N.E.; Zhou, Q.T.; Singh, S.K.; Nema, S.; Topp, E.M. Effects of drying process on an IgG1 monoclonal antibody using solid-state Hydrogen Deuterium Exchange with Mass Spectrometric analysis (ssHDX-MS). Pharm. Res., 2018, 35(35), 12.
[126]
Moorthy, B.S.; Zarraga, I.E.; Kumar, L.; Walters, B.T.; Goldbach, P.; Topp, E.M.; Allmendinger, A. Solid-state hydrogen-deuterium exchange mass spectrometry: Correlation of deuterium uptake and long-term stability of lyophilized monoclonal antibody formulations. Mol. Pharm., 2018, 15(1), 1-11.
[127]
Sharma, V.K.; Patapoff, T.W.; Kabakoff, B.; Pai, S.; Hilario, E.; Zhang, B.; Li, C.; Borisov, O.; Kelley, R.F.; Chorny, I.; Zhou, J.Z.; Dill, K.A.; Swartz, T.E. In silico selection of therapeutic antibodies for development: Viscosity, clearance, and chemical stability. Proc. Natl. Acad. Sci. USA, 2014, 111(52), 18601-18606.
[128]
Chaudhri, A.; Zarraga, I.E.; Yadav, S.; Patapoff, T.W.; Shire, S.J.; Voth, G.A. The role of amino acid sequence in the self-association of therapeutic monoclonal antibodies: Insights from coarse-grained modeling. J. Phys. Chem. B, 2013, 117(5), 1269-1279.
[129]
Hofmann, M.; Gieseler, H. Predictive screening tools used in high-concentration protein formulation development. J. Pharm. Sci., 2017, •••
[http://dx.doi.org/10.1016/j.xphs.2017.10.036]
[http://dx.doi.org/10.1016/j.xphs.2017.10.036]
[130]
Kuhn, A.B.; Kube, S.; Karow-Zwick, A.R.; Seeliger, D.; Garidel, P.; Blech, M.; Schafer, L.V. Improved solution-state properties of monoclonal antibodies by targeted mutations. J. Phys. Chem. B, 2017, 121(48), 10818-10827.
[131]
Chennamsetty, N.; Voynov, V.; Kayser, V.; Helk, B.; Trout, B.L. Design of therapeutic proteins with enhanced stability. Proc. Natl. Acad. Sci. USA, 2009, 106(29), 11937-11942.
[132]
Watson, C.; Sharp, J.S. Conformational analysis of therapeutic proteins by hydroxyl radical protein footprinting. AAPS J., 2012, 14(2), 206-217.
[133]
Deperalta, G.; Alvarez, M.; Bechtel, C.; Dong, K.; McDonald, R.; Ling, V. Structural analysis of a therapeutic monoclonal antibody dimer by hydroxyl radical footprinting. MAbs, 2013, 5(1), 86-101.
[134]
Jones, L.M.; Zhang, H.; Cui, W.D.; Kumar, S.; Sperry, J.B.; Carroll, J.A.; Gross, M.L. Complementary MS methods assist conformational characterization of antibodies with altered S-S bonding networks. J. Am. Soc. Mass Spectrom., 2013, 24(6), 835-845.
[135]
Beck, A.; Wurch, T.; Bailly, C.; Corvaia, N. Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol., 2010, 10(5), 345-352.
[136]
Salfeld, J.G. Isotype selection in antibody engineering. Nat. Biotechnol., 2007, 25(12), 1369-1372.
[137]
Jhan, S.Y.; Huang, L.J.; Wang, T.F.; Chou, H.H.; Chen, S.H. Dimethyl labeling coupled with mass spectrometry for topographical characterization of primary amines on monoclonal antibodies. Anal. Chem., 2017, 89(7), 4255-4263.
Related Books
Aromatherapy: The Science of Essential Oils
In Vitro Propagation and Secondary Metabolite Production from Medicinal Plants: Current Trends (Part 2)
Micropropagation of Medicinal Plants
Software and Programming Tools in Pharmaceutical Research
Biotechnology and Drug Development for Targeting Human Diseases
In Vitro Propagation and Secondary Metabolite Production from Medicinal Plants: Current Trends (Part 1)
Molecular and Physiological Insights into Plant Stress Tolerance and Applications in Agriculture- Part 2
Micropropagation of Medicinal Plants
Genome Editing in Bacteria (Part 1)
Data Science for Agricultural Innovation and Productivity
Article Metrics
70
5