Skip to main content
SpringerLink
Log in
Book cover

Biobetters pp 137–151Cite as

Oxidation of Proteins in the In Vivo Environment: What We Know; What We Need to Study and Potential Mitigation Strategies

  • Chapter

  • 1629 Accesses

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 19))

Abstract

The oxidation of proteins in vivo continues to be an important focus of biomedical research (Davies 2005) as elevated levels of oxidized proteins have been associated with a large number of pathologies (Guttmann and Ghoshal 2011; Martinez et al. 2010; Nakamura et al. 2012) as well as biological aging (Stadtman 1988, 1992; Oliver et al. 1987). Protein oxidation can lead to changes in activity, conformation, protein–protein interactions, and half-life (Stadtman and Oliver 1991; Levine et al. 1981; Bota and Davies 2002; Davies and Lin 1988; Davies et al. 1987a, b; Davies and Delsignore 1987; Davies 1987), and trigger autophagy and/or apoptosis (Chan et al. 2012; Dunlop et al. 2011). An important consequence of oxidative (and other) covalent protein modifications can be the potential immunogenicity of the modified proteins (Eggleton et al. 2013), especially if antibodies directed against neo-epitopes cross-react with native, unmodified proteins, breaking immune tolerance (Griffiths 2008; Omersel et al. 2008, 2011; van Beers et al. 2011; Sauerborn et al. 2010; Jiskoot et al. 2009; Schellekens and Jiskoot 2006). Here, autoantibody generation may lead to autoimmune disorders. Analogous to endogenous proteins, therapeutic proteins may be subject to oxidation in vivo (i.e., after administration to the patient) though potential oxidation reactions of therapeutic proteins in vivo will likely be restricted to the extracellular space. The potential for immunogenicity is, therefore, not only an issue for endogenous proteins but also for the development and safe delivery of protein therapeutics (van Beers et al. 2011; Sauerborn et al. 2010; Jiskoot et al. 2009; Schellekens and Jiskoot 2006).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Bartesaghi S, Wenzel J, Trujillo M, Lopez M, Joseph J, Kalyanaraman B, Radi R (2010) Lipid peroxyl radicals mediate tyrosine dimerization and nitration in membranes. Chem Res Toxicol 23:821–835. doi:10.1021/tx900446r

    PubMed Central  CAS  PubMed  Google Scholar 

  • Battersby JE, Mukku VR, Clark RG, Hancock WS (1995) Affinity purification and microcharacterization of recombinant DNA-derived human growth hormone isolated from an in vivo model. Anal Chem 67:447–455

    CAS  PubMed  Google Scholar 

  • Battistuzzi G, Bellei M, Bortolotti CA, Sola M (2010) Redox properties of heme peroxidases. Arch Biochem Biophys 500:21–36. doi:10.1016/j.abb.2010.03.002

    CAS  PubMed  Google Scholar 

  • Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437

    CAS  PubMed  Google Scholar 

  • Bergt C, Fu X, Huq NP, Kao J, Heinecke JW (2004) Lysine residues direct the chlorination of tyrosines in YXXK motifs of apolipoprotein A-I when hypochlorous acid oxidizes high density lipoprotein. J Biol Chem 279:7856–7866. doi:10.1074/jbc.M309046200

    CAS  PubMed  Google Scholar 

  • Bertolotti-Ciarlet A, Wang W, Lownes R, Pristatsky P, Fang Y, McKelvey T, Li Y, Drummond J, Prueksaritanont T, Vlasak J (2009) Impact of methionine oxidation on the binding of human IgG1 to Fc Rn and Fc gamma receptors. Mol Immunol 46:1878–1882. doi:10.1016/j.molimm.2009.02.002

    CAS  PubMed  Google Scholar 

  • Birtalan S, Zhang Y, Fellouse FA, Shao L, Schaefer G, Sidhu SS (2008) The intrinsic contributions of tyrosine, serine, glycine and arginine to the affinity and specificity of antibodies. J Mol Biol 377:1518–1528. doi:10.1016/j.jmb.2008.01.093

    CAS  PubMed  Google Scholar 

  • Boccini F, Herold S (2004) Mechanistic studies of the oxidation of oxyhemoglobin by peroxynitrite. Biochemistry 43:16393–16404. doi:10.1021/bi0482250

    CAS  PubMed  Google Scholar 

  • Bota DA, Davies KJ (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat Cell Biol 4:674–680. doi:10.1038/ncb836

    CAS  PubMed  Google Scholar 

  • Brych SR, Gokarn YR, Hultgen H, Stevenson RJ, Rajan R, Matsumura M (2010) Characterization of antibody aggregation: role of buried, unpaired cysteines in particle formation. J Pharm Sci 99:764–781. doi:10.1002/jps.21868

    CAS  PubMed  Google Scholar 

  • Candeias LP, Patel KB, Stratford MR, Wardman P (1993) Free hydroxyl radicals are formed on reaction between the neutrophil-derived species superoxide anion and hypochlorous acid. FEBS Lett 333:151–153

    CAS  PubMed  Google Scholar 

  • Cappadona S, Baker PR, Cutillas PR, Heck AJ, van Breukelen B (2012) Current challenges in software solutions for mass spectrometry-based quantitative proteomics. Amino Acids 43:1087–1108. doi:10.1007/s00726-012-1289-8

    PubMed Central  CAS  PubMed  Google Scholar 

  • Carballal S, Bartesaghi S, Radi R (2013) Kinetic and mechanistic considerations to assess the biological fate of peroxynitrite. Biochim Biophys Acta. doi:10.1016/j.bbagen.2013.07.005

    PubMed Central  PubMed  Google Scholar 

  • Chan SW, Dunlop RA, Rowe A, Double KL, Rodgers KJ (2012) L-DOPA is incorporated into brain proteins of patients treated for Parkinson’s disease, inducing toxicity in human neuroblastoma cells in vitro. Exp Neurol 238:29–37. doi:10.1016/j.expneurol.2011.09.029

    CAS  PubMed  Google Scholar 

  • Correia IR (2010) Stability of IgG isotypes in serum. MAbs 2:221–232

    PubMed Central  PubMed  Google Scholar 

  • Crane FL, Low H (2008) Reactive oxygen species generation at the plasma membrane for antibody control. Autoimmun Rev 7:518–522. doi:10.1016/j.autrev.2008.04.004

    CAS  PubMed  Google Scholar 

  • Dalle-Donne I, Scaloni A, Giustarini D, Cavarra E, Tell G, Lungarella G, Colombo R, Rossi R, Milzani A (2005) Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics. Mass Spectrom Rev 24:55–99. doi:10.1002/mas.20006

    CAS  PubMed  Google Scholar 

  • Davies KJ (1987) Protein damage and degradation by oxygen radicals. I. General aspects. J Biol Chem 262:9895–9901

    CAS  PubMed  Google Scholar 

  • Davies MJ (2005) The oxidative environment and protein damage. Biochim Biophys Acta 1703:93–109. doi:10.1016/j.bbapap.2004.08.007

    CAS  PubMed  Google Scholar 

  • Davies KJ, Delsignore ME (1987) Protein damage and degradation by oxygen radicals. III. Modification of secondary and tertiary structure. J Biol Chem 262:9908–9913

    CAS  PubMed  Google Scholar 

  • Davies KJ, Lin SW (1988) Oxidatively denatured proteins are degraded by an ATP-independent proteolytic pathway in Escherichia coli. Free Radic Biol Med 5:225–236

    CAS  PubMed  Google Scholar 

  • Davies KJ, Lin SW, Pacifici RE (1987a) Protein damage and degradation by oxygen radicals. IV. Degradation of denatured protein. J Biol Chem 262:9914–9920

    CAS  PubMed  Google Scholar 

  • Davies KJ, Delsignore ME, Lin SW (1987b) Protein damage and degradation by oxygen radicals. II. Modification of amino acids. J Biol Chem 262:9902–9907

    CAS  PubMed  Google Scholar 

  • Demartini DR, Pasquali G, Carlini CR (2013) An overview of proteomics approaches applied to biopharmaceuticals and cyclotides research. J Proteomics. doi:10.1016/j.jprot.2013.06.009

    PubMed  Google Scholar 

  • Denicola A, Souza JM, Radi R (1998) Diffusion of peroxynitrite across erythrocyte membranes. Proc Natl Acad Sci U S A 95:3566–3571

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dunlop RA, Brunk UT, Rodgers KJ (2011) Proteins containing oxidized amino acids induce apoptosis in human monocytes. Biochem J 435:207–216. doi:10.1042/BJ20100682

    CAS  PubMed  Google Scholar 

  • Eggleton P, Nissim A, Ryan BJ, Whiteman M, Winyard PG (2013) Detection and isolation of human serum autoantibodies that recognize oxidatively modified autoantigens. Free Radic Biol Med 57:79–91. doi:10.1016/j.freeradbiomed.2012.11.006

    CAS  PubMed  Google Scholar 

  • Fellouse FA, Li B, Compaan DM, Peden AA, Hymowitz SG, Sidhu SS (2005) Molecular recognition by a binary code. J Mol Biol 348:1153–1162. doi:10.1016/j.jmb.2005.03.041

    CAS  PubMed  Google Scholar 

  • Friedman M (1999) Chemistry, biochemistry, nutrition, and microbiology of lysinoalanine, lanthionine, and histidinoalanine in food and other proteins. J Agric Food Chem 47:1295–1319

    CAS  PubMed  Google Scholar 

  • Fu X, Mueller DM, Heinecke JW (2002) Generation of intramolecular and intermolecular sulfenamides, sulfinamides, and sulfonamides by hypochlorous acid: a potential pathway for oxidative cross-linking of low-density lipoprotein by myeloperoxidase. Biochemistry 41:1293–1301

    CAS  PubMed  Google Scholar 

  • Garrison WM (1987) Reaction-mechanisms in the radiolysis of peptides, polypeptides, and proteins. Chem Rev 87:381–398

    CAS  Google Scholar 

  • Gaza-Bulseco G, Faldu S, Hurkmans K, Chumsae C, Liu H (2008) Effect of methionine oxidation of a recombinant monoclonal antibody on the binding affinity to protein A and protein G. J Chromatogr B Analyt Technol Biomed Life Sci 870:55–62. doi:10.1016/j.jchromb.2008.05.045

    CAS  PubMed  Google Scholar 

  • Giulivi C, Davies KJ (1994) Dityrosine: a marker for oxidatively modified proteins and selective proteolysis. Methods Enzymol 233:363–371

    CAS  PubMed  Google Scholar 

  • Giulivi C, Traaseth NJ, Davies KJ (2003) Tyrosine oxidation products: analysis and biological relevance. Amino Acids 25:227–232. doi:10.1007/s00726-003-0013-0

    CAS  PubMed  Google Scholar 

  • Goldstein S, Meyerstein D, Czapski G (1993) The Fenton reagents. Free Radic Biol Med 15:435–445

    CAS  PubMed  Google Scholar 

  • Griffiths HR (2008) Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease? Autoimmun Rev 7:544–549. doi:10.1016/j.autrev.2008.04.013

    CAS  PubMed  Google Scholar 

  • Griffiths HR, Lunec J (1996) The C1q binding activity of IgG is modified in vitro by reactive oxygen species: implications for rheumatoid arthritis. FEBS Lett 388:161–164

    CAS  PubMed  Google Scholar 

  • Guttmann RP, Ghoshal S (2011) Thiol-protease oxidation in age-related neuropathology. Free Radic Biol Med 51:282–288. doi:10.1016/j.freeradbiomed.2011.04.017

    CAS  PubMed  Google Scholar 

  • Hawkins CL, Davies MJ (1998) Hypochlorite-induced damage to proteins: formation of nitrogen-centred radicals from lysine residues and their role in protein fragmentation. Biochem J 332(Pt 3):617–625

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hawkins CL, Davies MJ (1999) Hypochlorite-induced oxidation of proteins in plasma: formation of chloramines and nitrogen-centred radicals and their role in protein fragmentation. Biochem J 340(Pt 2):539–548

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hazen SL, Heinecke JW (1997) 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest 99:2075–2081. doi:10.1172/JCI119379

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hensel M, Steurer R, Fichtl J, Elger C, Wedekind F, Petzold A, Schlothauer T, Molhoj M, Reusch D, Bulau P (2011) Identification of potential sites for tryptophan oxidation in recombinant antibodies using tert-butylhydroperoxide and quantitative LC-MS. PLoS One 6:e17708. doi:10.1371/journal.pone.0017708

    PubMed Central  CAS  PubMed  Google Scholar 

  • Herold S, Shivashankar K (2003) Metmyoglobin and methemoglobin catalyze the isomerization of peroxynitrite to nitrate. Biochemistry 42:14036–14046. doi:10.1021/bi0350349

    CAS  PubMed  Google Scholar 

  • Hildenbrand K, Schulte-Frohlinde D (1997) Time-resolved EPR studies on the reaction rates of peroxyl radicals of poly(acrylic acid) and of calf thymus DNA with glutathione. Re-examination of a rate constant for DNA. Int J Radiat Biol 71:377–385

    CAS  PubMed  Google Scholar 

  • Himmelfarb J, McMenamin ME, Loseto G, Heinecke JW (2001) Myeloperoxidase-catalyzed 3-chlorotyrosine formation in dialysis patients. Free Radic Biol Med 31:1163–1169

    CAS  PubMed  Google Scholar 

  • Honda K, Ono M, Shitashige M, Masuda M, Kamita M, Miura N, Yamada T (2013) Proteomic approaches to the discovery of cancer biomarkers for early detection and personalized medicine. Jpn J Clin Oncol 43:103–109. doi:10.1093/jjco/hys200

    PubMed  Google Scholar 

  • Indovina P, Marcelli E, Pentimalli F, Tanganelli P, Tarro G, Giordano A (2013) Mass spectrometry-based proteomics: the road to lung cancer biomarker discovery. Mass Spectrom Rev 32:129–142. doi:10.1002/mas.21355

    CAS  PubMed  Google Scholar 

  • Ingold KU (1969) Peroxy radicals. Acc Chem Res 2:1–9

    CAS  Google Scholar 

  • Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS (1992) Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 298:431–437

    CAS  PubMed  Google Scholar 

  • Jiskoot W, van Schie RM, Carstens MG, Schellekens H (2009) Immunological risk of injectable drug delivery systems. Pharm Res 26:1303–1314. doi:10.1007/s11095-009-9855-9

    CAS  PubMed  Google Scholar 

  • Kissner R, Nauser T, Kurz C, Koppenol WH (2003) Peroxynitrous acid–where is the hydroxyl radical? IUBMB Life 55:567–572

    CAS  PubMed  Google Scholar 

  • Koppenol WH (1993) The centennial of the Fenton reaction. Free Radic Biol Med 15:645–651

    CAS  PubMed  Google Scholar 

  • Koppenol WH, Kissner R (1998) Can O = NOOH undergo homolysis? Chem Res Toxicol 11:87–90. doi:10.1021/tx970200x

    CAS  PubMed  Google Scholar 

  • Lai ZW, Nice EC, Schilling O (2013) Glycocapture-based proteomics for secretome analysis. Proteomics 13:512–525. doi:10.1002/pmic.201200414

    CAS  PubMed  Google Scholar 

  • Lalowski M, Magni F, Mainini V, Monogioudi E, Gotsopoulos A, Soliymani R, Chinello C, Baumann M (2013) Imaging mass spectrometry: a new tool for kidney disease investigations. Nephrol Dial Transplant 28:1648–1656. doi:10.1093/ndt/gft008

    PubMed  Google Scholar 

  • Lam SW, Jimenez CR, Boven E (2013) Breast cancer classification by proteomic technologies: current state of knowledge. Cancer Treat Rev. doi:10.1016/j.ctrv.2013.06.006

    PubMed  Google Scholar 

  • Langkammer C, Ropele S, Pirpamer L, Fazekas F, Schmidt R (2013) MRI for iron mapping in Alzheimer’s disease. Neurodegener Dis. doi:10.1159/000353756

    PubMed  Google Scholar 

  • Levine RL, Oliver CN, Fulks RM, Stadtman ER (1981) Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis. Proc Natl Acad Sci U S A 78:2120–2124

    PubMed Central  CAS  PubMed  Google Scholar 

  • Litwin T, Gromadzka G, Szpak GM, Jablonka-Salach K, Bulska E, Czlonkowska A (2013) Brain metal accumulation in Wilson’s disease. J Neurol Sci 329:55–58. doi:10.1016/j.jns.2013.03.021

    CAS  PubMed  Google Scholar 

  • Liu D, Ren D, Huang H, Dankberg J, Rosenfeld R, Cocco MJ, Li L, Brems DN, Remmele RL Jr (2008) Structure and stability changes of human IgG1 Fc as a consequence of methionine oxidation. Biochemistry 47:5088–5100. doi:10.1021/bi702238b

    CAS  PubMed  Google Scholar 

  • Loew C, Knoblich C, Fichtl J, Alt N, Diepold K, Bulau P, Goldbach P, Adler M, Mahler HC, Grauschopf U (2012) Analytical protein a chromatography as a quantitative tool for the screening of methionine oxidation in monoclonal antibodies. J Pharm Sci 101:4248–4257. doi:10.1002/jps.23286

    CAS  PubMed  Google Scholar 

  • Luo Q, Joubert MK, Stevenson R, Ketchem RR, Narhi LO, Wypych J (2011) Chemical modifications in therapeutic protein aggregates generated under different stress conditions. J Biol Chem 286:25134–25144. doi:10.1074/jbc.M110.160440

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lymar SV, Hurst JK (1996) Carbon dioxide: physiological catalyst for peroxynitrite-mediated cellular damage or cellular protectant? Chem Res Toxicol 9:845–850. doi:10.1021/tx960046z

    CAS  PubMed  Google Scholar 

  • Lymar SV, Jiang Q, Hurst JK (1996) Mechanism of carbon dioxide-catalyzed oxidation of tyrosine by peroxynitrite. Biochemistry 35:7855–7861. doi:10.1021/bi960331h

    CAS  PubMed  Google Scholar 

  • Ma YS, Chao CC, Stadtman ER (1999) Oxidative modification of glutamine synthetase by 2,2′-azobis(2- amidinopropane) dihydrochloride. Arch Biochem Biophys 363:129–134. doi:10.1006/abbi.1998.1076

    CAS  PubMed  Google Scholar 

  • Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS (2010) Stability of protein pharmaceuticals: an update. Pharm Res 27:544–575. doi:10.1007/s11095-009-0045-6

    PubMed  Google Scholar 

  • Marla SS, Lee J, Groves JT (1997) Peroxynitrite rapidly permeates phospholipid membranes. Proc Natl Acad Sci U S A 94:14243–14248

    PubMed Central  CAS  PubMed  Google Scholar 

  • Martinez A, Portero-Otin M, Pamplona R, Ferrer I (2010) Protein targets of oxidative damage in human neurodegenerative diseases with abnormal protein aggregates. Brain Pathol 20:281–297. doi:10.1111/j.1750-3639.2009.00326.x

    CAS  PubMed  Google Scholar 

  • McIntyre JA, Wagenknecht DR, Faulk WP (2006) Redox-reactive autoantibodies: detection and physiological relevance. Autoimmun Rev 5:76–83. doi:10.1016/j.autrev.2005.07.009

    CAS  PubMed  Google Scholar 

  • Mehl M, Daiber A, Herold S, Shoun H, Ullrich V (1999) Peroxynitrite reaction with heme proteins. Nitric Oxide 3:142–152. doi:10.1006/niox.1999.0217

    CAS  PubMed  Google Scholar 

  • Merenyi G, Lind J (1998) Free radical formation in the peroxynitrous acid (ONOOH)/peroxynitrite (ONOO-) system. Chem Res Toxicol 11:243–246. doi:10.1021/tx980026s

    CAS  PubMed  Google Scholar 

  • Merenyi G, Lind J, Goldstein S, Czapski G (1998) Peroxynitrous acid homolyzes into *OH and *NO2 radicals. Chem Res Toxicol 11:712–713. doi:10.1021/tx980043h

    CAS  PubMed  Google Scholar 

  • Moller MN, Hatch DM, Kim HY, Porter NA (2012) Superoxide reaction with tyrosyl radicals generates para-hydroperoxy and para-hydroxy derivatives of tyrosine. J Am Chem Soc 134:16773–16780. doi:10.1021/ja307215z

    CAS  PubMed  Google Scholar 

  • Mozziconacci O, Kerwin BA, Schoneich C (2010a) Reversible hydrogen transfer between cysteine thiyl radical and glycine and alanine in model peptides: covalent H/D exchange, radical-radical reactions, and L- to D-Ala conversion. J Phys Chem B 114:6751–6762. doi:10.1021/jp101508b

    CAS  PubMed  Google Scholar 

  • Mozziconacci O, Kerwin BA, Schoneich C (2010b) Photolysis of an intrachain peptide disulfide bond: primary and secondary processes, formation of H2S, and hydrogen transfer reactions. J Phys Chem B 114:3668–3688. doi:10.1021/jp910789x

    CAS  PubMed  Google Scholar 

  • Mozziconacci O, Kerwin BA, Schoneich C (2011) Reversible hydrogen transfer reactions of cysteine thiyl radicals in peptides: the conversion of cysteine into dehydroalanine and alanine, and of alanine into dehydroalanine. J Phys Chem B 115:12287–12305. doi:10.1021/jp2070453

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mozziconacci O, Williams TD, Schoneich C (2012) Intramolecular hydrogen transfer reactions of thiyl radicals from glutathione: formation of carbon-centered radical at Glu, Cys, and Gly. Chem Res Toxicol 25:1842–1861. doi:10.1021/tx3000494

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nagy P, Kettle AJ, Winterbourn CC (2009) Superoxide-mediated formation of tyrosine hydroperoxides and methionine sulfoxide in peptides through radical addition and intramolecular oxygen transfer. J Biol Chem 284:14723–14733. doi:10.1074/jbc.M809396200

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nakamura T, Cho DH, Lipton SA (2012) Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases. Exp Neurol 238:12–21. doi:10.1016/j.expneurol.2012.06.032

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nauser T, Schoneich C (2003) Thiyl radicals abstract hydrogen atoms from the (alpha)C-H bonds in model peptides: absolute rate constants and effect of amino acid structure. J Am Chem Soc 125:2042–2043. doi:10.1021/ja0293599

    CAS  PubMed  Google Scholar 

  • Nauser T, Pelling J, Schoneich C (2004) Thiyl radical reaction with amino acid side chains: rate constants for hydrogen transfer and relevance for posttranslational protein modification. Chem Res Toxicol 17:1323–1328. doi:10.1021/tx049856y

    CAS  PubMed  Google Scholar 

  • Nauser T, Koppenol WH, Schoneich C (2012) Reversible hydrogen transfer reactions in thiyl radicals from cysteine and related molecules: absolute kinetics and equilibrium constants determined by pulse radiolysis. J Phys Chem B 116:5329–5341. doi:10.1021/jp210954v

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nikolaidis MG, Jamurtas AZ (2009) Blood as a reactive species generator and redox status regulator during exercise. Arch Biochem Biophys 490:77–84. doi:10.1016/j.abb.2009.08.015

    CAS  PubMed  Google Scholar 

  • Nuriel T, Hansler A, Gross SS (2011) Protein nitrotryptophan: formation, significance and identification. J Proteomics 74:2300–2312. doi:10.1016/j.jprot.2011.05.032

    PubMed Central  CAS  PubMed  Google Scholar 

  • Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER (1987) Age-related changes in oxidized proteins. J Biol Chem 262:5488–5491

    CAS  PubMed  Google Scholar 

  • Omersel J, Jurgec I, Cucnik S, Kveder T, Rozman B, Sodin-Semrl S, Bozic B (2008) Autoimmune and proinflammatory activity of oxidized immunoglobulins. Autoimmun Rev 7:523–529. doi:10.1016/j.autrev.2008.04.005

    CAS  PubMed  Google Scholar 

  • Omersel J, Avbersek-Luznik I, Grabnar PA, Kveder T, Rozman B, Bozic B (2011) Autoimmune reactivity of IgM acquired after oxidation. Redox Rep 16:248–256. doi:10.1179/174329211X13190184351680

    CAS  PubMed  Google Scholar 

  • Parker SJ, Koistinaho J, White AR, Kanninen KM (2013) Biometals in rare neurodegenerative disorders of childhood. Front Aging Neurosci 5:14. doi:10.3389/fnagi.2013.00014

    PubMed Central  PubMed  Google Scholar 

  • Pattison DI, O’Reilly RJ, Skaff O, Radom L, Anderson RF, Davies MJ (2011) One-electron reduction of N-chlorinated and N-brominated species is a source of radicals and bromine atom formation. Chem Res Toxicol 24:371–382. doi:10.1021/tx100325z

    CAS  PubMed  Google Scholar 

  • Pryor WA, Lemercier JN, Zhang H, Uppu RM, Squadrito GL (1997) The catalytic role of carbon dioxide in the decomposition of peroxynitrite. Free Radic Biol Med 23:331–338

    CAS  PubMed  Google Scholar 

  • Radi R (2013) Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res 46:550–559. doi:10.1021/ar300234c

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ratnayake S, Dias IH, Lattman E, Griffiths HR (2013) Stabilising cysteinyl thiol oxidation and nitrosation for proteomic analysis. J Proteomics. doi:10.1016/j.jprot.2013.06.019

    PubMed  Google Scholar 

  • Rees MD, Kennett EC, Whitelock JM, Davies MJ (2008) Oxidative damage to extracellular matrix and its role in human pathologies. Free Radic Biol Med 44:1973–2001. doi:10.1016/j.freeradbiomed.2008.03.016

    CAS  PubMed  Google Scholar 

  • Richardson DE, Regino CA, Yao H, Johnson JV (2003) Methionine oxidation by peroxymonocarbonate, a reactive oxygen species formed from CO2/bicarbonate and hydrogen peroxide. Free Radic Biol Med 35:1538–1550

    CAS  PubMed  Google Scholar 

  • Sauerborn M, Brinks V, Jiskoot W, Schellekens H (2010) Immunological mechanism underlying the immune response to recombinant human protein therapeutics. Trends Pharmacol Sci 31:53–59. doi:10.1016/j.tips.2009.11.001

    CAS  PubMed  Google Scholar 

  • Schellekens H, Jiskoot W (2006) Erythropoietin-associated PRCA: still an unsolved mystery. J Immunotoxicol 3:123–130. doi:10.1080/15476910600845567

    CAS  PubMed  Google Scholar 

  • Schoneich C (2005) Methionine oxidation by reactive oxygen species: reaction mechanisms and relevance to Alzheimer’s disease. Biochim Biophys Acta 1703:111–119. doi:10.1016/j.bbapap.2004.09.009

    PubMed  Google Scholar 

  • Shchepin R, Moller MN, Kim HY, Hatch DM, Bartesaghi S, Kalyanaraman B, Radi R, Porter NA (2010) Tyrosine-lipid peroxide adducts from radical termination: para coupling and intramolecular Diels-Alder cyclization. J Am Chem Soc 132:17490–17500. doi:10.1021/ja106503a

    PubMed Central  CAS  PubMed  Google Scholar 

  • Stadtman ER (1988) Protein modification in aging. J Gerontol 43:B112–B120

    CAS  PubMed  Google Scholar 

  • Stadtman ER (1990) Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med 9:315–325

    CAS  PubMed  Google Scholar 

  • Stadtman ER (1992) Protein oxidation and aging. Science 257:1220–1224

    CAS  PubMed  Google Scholar 

  • Stadtman ER, Berlett BS (1991) Fenton chemistry. Amino acid oxidation. J Biol Chem 266:17201–17211

    CAS  PubMed  Google Scholar 

  • Stadtman ER, Oliver CN (1991) Metal-catalyzed oxidation of proteins. Physiological consequences. J Biol Chem 266:2005–2008

    CAS  PubMed  Google Scholar 

  • Steinmann D, Ji JA, Wang YJ, Schoneich C (2012) Oxidation of human growth hormone by oxygen-centered radicals: formation of Leu-101 hydroperoxide and Tyr-103 oxidation products. Mol Pharm 9:803–814. doi:10.1021/mp3001028

    CAS  PubMed  Google Scholar 

  • Szweda LI, Stadtman ER (1992) Iron-catalyzed oxidative modification of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides. Structural and functional changes. J Biol Chem 267:3096–3100

    CAS  PubMed  Google Scholar 

  • Taba P (2013) Metals and movement disorders. Curr Opin Neurol 26:435–441. doi:10.1097/WCO.0b013e3283629beb

    CAS  PubMed  Google Scholar 

  • Torosantucci R, Sharov VS, van Beers M, Brinks V, Schoneich C, Jiskoot W (2013) Identification of oxidation sites and covalent cross-links in metal catalyzed oxidized interferon Beta-1a: potential implications for protein aggregation and immunogenicity. Mol Pharm 10:2311–2322. doi:10.1021/mp300665u

    PubMed Central  CAS  PubMed  Google Scholar 

  • Uppu RM, Squadrito GL, Pryor WA (1996) Acceleration of peroxynitrite oxidations by carbon dioxide. Arch Biochem Biophys 327:335–343. doi:10.1006/abbi.1996.0131

    CAS  PubMed  Google Scholar 

  • van Beers MM, Sauerborn M, Gilli F, Brinks V, Schellekens H, Jiskoot W (2011) Oxidized and aggregated recombinant human interferon beta is immunogenic in human interferon beta transgenic mice. Pharm Res 28:2393–2402. doi:10.1007/s11095-011-0451-4

    PubMed Central  PubMed  Google Scholar 

  • Viner RI, Krainev AG, Williams TD, Schoneich C, Bigelow DJ (1997) Identification of oxidation-sensitive peptides within the cytoplasmic domain of the sarcoplasmic reticulum Ca2 + −ATPase. Biochemistry 36:7706–7716. doi:10.1021/bi970058z

    CAS  PubMed  Google Scholar 

  • Wang W, Vlasak J, Li Y, Pristatsky P, Fang Y, Pittman T, Roman J, Wang Y, Prueksaritanont T, Ionescu R (2011) Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol 48:860–866. doi:10.1016/j.molimm.2010.12.009

    CAS  PubMed  Google Scholar 

  • Williams R, Buchheit CL, Berman NE, LeVine SM (2012) Pathogenic implications of iron accumulation in multiple sclerosis. J Neurochem 120:7–25. doi:10.1111/j.1471-4159.2011.07536.x

    PubMed Central  CAS  PubMed  Google Scholar 

  • Winterbourn CC, Parsons-Mair HN, Gebicki S, Gebicki JM, Davies MJ (2004) Requirements for superoxide-dependent tyrosine hydroperoxide formation in peptides. Biochem J 381:241–248. doi:10.1042/BJ20040259

    PubMed Central  CAS  PubMed  Google Scholar 

  • Witze ES, Old WM, Resing KA, Ahn NG (2007) Mapping protein post-translational modifications with mass spectrometry. Nat Methods 4:798–806. doi:10.1038/nmeth1100

    CAS  PubMed  Google Scholar 

  • Ye JD, Tereshko V, Frederiksen JK, Koide A, Fellouse FA, Sidhu SS, Koide S, Kossiakoff AA, Piccirilli JA (2008) Synthetic antibodies for specific recognition and crystallization of structured RNA. Proc Natl Acad Sci U S A 105:82–87. doi:10.1073/pnas.0709082105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yin S, Pastuskovas CV, Khawli LA, Stults JT (2013) Characterization of therapeutic monoclonal antibodies reveals differences between in vitro and in vivo time-course studies. Pharm Res 30:167–178. doi:10.1007/s11095-012-0860-z

    CAS  PubMed  Google Scholar 

  • Yoo EM, Wims LA, Chan LA, Morrison SL (2003) Human IgG2 can form covalent dimers. J Immunol 170:3134–3138

    CAS  PubMed  Google Scholar 

  • Zhang W, Czupryn MJ (2002) Free sulfhydryl in recombinant monoclonal antibodies. Biotechnol Prog 18:509–513. doi:10.1021/bp025511z

    PubMed  Google Scholar 

  • Zhang Q, Schenauer MR, McCarter JD, Flynn GC (2013) IgG1 thioether bond formation in vivo. J Biol Chem 288:16371–16382. doi:10.1074/jbc.M113.468397

    PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao F, Ghezzo-Schoneich E, Aced GI, Hong J, Milby T, Schoneich C (1997) Metal-catalyzed oxidation of histidine in human growth hormone. Mechanism, isotope effects, and inhibition by a mild denaturing alcohol. J Biol Chem 272:9019–9029

    CAS  PubMed  Google Scholar 

  • Zhou S, Mozziconacci O, Kerwin BA, Schoneich C (2013) Fluorogenic tagging methodology applied to characterize oxidized tyrosine and phenylalanine in an immunoglobulin monoclonal antibody. Pharm Res 30:1311–1327. doi:10.1007/s11095-012-0970-7

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, KS, 66047, USA

    Christian Schöneich

Authors
  1. Christian Schöneich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Schöneich .

Editor information

Editors and Affiliations

  1. Centre for Drug Evaluation and Research, Food and Drug Administration, Division of Biotechnology Review and Research III, Office of Biotechnology Products, Silver Spring, Maryland, USA

    Amy Rosenberg

  2. Genentech, Inc., South San Francisco, California, USA

    Barthélemy Demeule

Rights and permissions

Reprints and permissions

Copyright information

© 2015 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Schöneich, C. (2015). Oxidation of Proteins in the In Vivo Environment: What We Know; What We Need to Study and Potential Mitigation Strategies. In: Rosenberg, A., Demeule, B. (eds) Biobetters. AAPS Advances in the Pharmaceutical Sciences Series, vol 19. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2543-8_9

Download citation

Publish with us

Policies and ethics

Search

Navigation