Oxidation of therapeutic proteins and peptides: Structural and biological consequences

Pharmaceutical Research

Volumn 31, Issue 3, 2014, Pages 541-553

  Torosantucci, Riccardo ^a   Schöneich, Christian ^b   Jiskoot, Wim ^a  

^a LEIDEN UNIVERSITY   (Netherlands)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

aggregation; immunogenicity; oxidation; peptides; proteins

Indexed keywords

ALBINTERFERON ALPHA2B; ALPHA INTERFERON; AMINO ACID; BETA INTERFERON; CALCITONIN; GRANULOCYTE COLONY STIMULATING FACTOR; GROWTH HORMONE; HUMAN GROWTH HORMONE; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2; INSULIN; MONOCLONAL ANTIBODY; OXYTOCIN; PARATHYROID HORMONE; PEGINTERFERON ALPHA2A; PEGINTERFERON BETA1A; PEPTIDE; PROTEIN; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RECOMBINANT PROTEIN;

CHEMICAL MODIFICATION; HUMAN; IMMUNOGENICITY; NONHUMAN; OXIDATION; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN STRUCTURE; REVIEW;

ANIMALS; ANTIBODIES, MONOCLONAL; CHEMISTRY, PHARMACEUTICAL; HUMANS; OXIDATION-REDUCTION; PEPTIDES; PROTEINS; RECOMBINANT PROTEINS;

EID: 84895502551     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-013-1199-9     Document Type: Review

References (132)

1. Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov. 2008;7:21-39.
2. Wang W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm. 1999;185:129-88.
3. Mohammadian-Mosaabadi J, Naderi-Manesh H, Maghsoudi N, Khalilzadeh R, Shojaosadati SA, Ebrahimi M. Effect of oxidative stress on the production of recombinant human interferon-gamma in Escherichia coli. Biotechnol Appl Biochem. 2005;41:37-42.
4. Krishnamurthy R, Madurawe RD, Bush KD, Lumpkin JA. Conditions Promoting Metal-Catalyzed Oxidations during Immobilized Cu-Iminodiacetic Acid Metal Affinity-Chromatography. Biotechnol Prog. 1995;11:643-50.
5. Kerwin BA. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: Structure and degradation pathways. J Pharm Sci. 2008;97:2924-35.
6. Takenawa T, Yokota A, Oda M, Takahashi H, Iwakura M. Protein oxidation during long storage: identification of the oxidation sites in dihydrofolate reductase from Escherichia coli through LC-MS and fragment studies. J Biochem. 2009;145:517-23.
7. Schöneich C, Barrón LB. Posttranslational Oxidative Modifications of Proteins. Encycl. of Anal. Chem. 2006.
8. Kerwin BA, Remmele Jr RL. Protect from light: photodegradation and protein biologics. J Pharm Sci. 2007;96:1468-79.
9. Torosantucci R, Mozziconacci O, Sharov V, Schöneich C, Jiskoot W. Chemical modifications in aggregates of recombinant human insulin induced by metal-catalyzed oxidation: covalent cross-linking via michael addition to tyrosine oxidation products. Pharm Res. 2012;29:2276-93.
10. Torosantucci R, Kükrer B, Mero A, Van Winsen M, Tantipolphan R, Jiskoot W. Plain and mono-pegylated recombinant human insulin exhibit similar stress-induced aggregation profiles. J Pharm Sci. 2011;100:2574-85.
11. Waterman KC, Adami RC, Alsante KM, Hong J, Landis MS, Lombardo F, et al. Stabilization of pharmaceuticals to oxidative degradation. Pharm Dev Technol. 2002;7:1-32.
12. Li S, Schöneich C, Borchardt RT. Chemical instability of protein pharmaceuticals: Mechanisms of oxidation and strategies for stabilization. Biotechnol Bioeng. 1995;48:490-500.
13. Stadtman ER, Berlett BS. Fenton chemistry.Amino acid oxidation. J Biol Chem. 1991;266:17201-11.
14. Stadtman ER. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med. 1990;9:315-25.
15. Stadtman ER. Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. Annu Rev Biochem. 1993;62:797-821.
16. Davies MJ. The oxidative environment and protein damage. Biochim Biophys Acta. 2005;1703:93-109.
17. Barelli S, Canellini G, Thadikkaran L, Crettaz D, Quadroni M, Rossier JS, et al. Oxidation of proteins: Basic principles and perspectives for blood proteomics. Proteomics Clin Appl. 2008;2:142-57.
18. Shacter E. Quantification and significance of protein oxidation in biological samples. Drug Metab Rev. 2000;32:307-26.
19. Cleland JL, Powell MF, Shire SJ. The Development of Stable Protein Formulations - a Close Look at Protein Aggregation, Deamidation, and Oxidation. Crit Rev Ther Drug Carrier Syst. 1993;10:307-77.
20. Kamionka M. Engineering of therapeutic proteins production in Escherichia coli. Curr Pharm Biotechnol. 2011;12:268-74.
21. Jayapal KR, Wlaschin KF, Hu WS, Yap MGS. Recombinant protein therapeutics from CHO cells - 20 years and counting. Chem Eng Prog. 2007;103:40-7.
22. Miyata T, Takizawa S, van Ypersele de Strihou C. Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets. Am J Physiol Cell Physiol. 2011;300:C226-31.
23. Row BW, Liu RG, Xu W, Kheirandish L, Gozal D. Intermittent hypoxia is associated with oxidative stress and spatial learning deficits in the rat. Am J Respir Crit Care Med. 2003;167:1548-53.
24. V. Pialoux, R. Mounier. Hypoxia-induced oxidative stress in health disorders. Oxid Med Cell Longev. 2012;940121.
25. Lin AA, Miller WM. CHO cell responses to low oxygen: regulation of oxygen consumption and sensitization to oxidative stress. Biotechnol Bioeng. 1992;40:505-16.
26. Yan BX, Yates Z, Balland A, Kleemann GR. Human IgG1 Hinge Fragmentation as the Result of H2O2-mediated Radical Cleavage. J Biol Chem. 2009;284:35390-402.
27. Wu Y, Levons J, Narang AS, Raghavan K, Rao VM. Reactive impurities in excipients: profiling, identification and mitigation of drug-excipient incompatibility. AAPS PharmSciTech. 2011;12:1248-63.
28. Maggio ET. Polysorbates, peroxides, protein aggregation, and immunogenicity:a growing concern. J of Excipients and Food Chem. 2012; 3:45-53.
29. Miller DM, Buettner GR, Aust SD. Transition-Metals as Catalysts of Autoxidation Reactions. Free Radic Biol Med. 1990;8:95-108.
30. Wu Y, Levons J, Narang AS, Raghavan K, Rao VM. Reactive impurities in excipients: profiling, identification and mitigation of drug-excipient incompatibility. AAPS PharmSciTech. 2011;12:1248-63.
31. Huang X, Atwood CS, Moir RD, Hartshorn MA, Tanzi RE, Bush AI. Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptides. J Biol Inorg Chem. 2004;9:954-60.
32. Lodovici M, Bigagli E. Oxidative stress and air pollution exposure. J Toxicol. 2011;487074.
33. Romieu I, Castro-Giner F, Kunzli N, Sunyer J. Air pollution, oxidative stress and dietary supplementation: a review. Eur Respir J. 2008;31:179-97.
34. Buettner GR, Jurkiewicz BA. Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat Res. 1996;145:532-41.
35. Ji JA, Zhang BY, Cheng W, Wang YJ. Methionine, Tryptophan, and Histidine Oxidation in a Model Protein, PTH: Mechanisms and Stabilization. J Pharm Sci. 2009;98:4485-500.
36. Rojas R, Apodaca G. Immunoglobulin transport across polarized epithelial cells. Nat Rev Mol Cell Biol. 2002;3:944-55.
37. An Z, Forrest G, Moore R, Cukan M, Haytko P, Huang L, et al. IgG2m4, an engineered antibody isotype with reduced Fc function. MAbs. 2009;1:572-9.
38. Al-Lazikani B, Lesk AM, Chothia C. Standard conformations for the canonical structures of immunoglobulins. J Mol Biol. 1997;273:927-48.
39. Pan H, Chen K, Chu L, Kinderman F, Apostol I, Huang G. Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn. Protein Sci. 2009;18:424-33.
40. Edelman GM, Cunningham BA, Gall WE, Gottlieb PD, Rutishauser U, Waxdal MJ. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci USA. 1969;63:78-85.
41. Rutishauser U, Cunningham BA, Bennett C, Konigsberg WH, Edelman GM. Amino acid sequence of the Fc region of a human gamma G-immunoglobulin. Proc Natl Acad Sci USA. 1968;61:1414-21.
42. van Loghem E. Allotypic markers. Monogr Allergy. 1986;19:40-51.
43. Khor HK, Jacoby ME, Squier TC, Chu GC, Chelius D. Identification of methionine sulfoxide diastereomers in immunoglobulin gamma antibodies using methionine sulfoxide reductase enzymes. MAbs. 2010;2:299-308.
44. Keck RG. The use of t-butyl hydroperoxide as a probe for methionine oxidation in proteins. Anal Biochem. 1996;236:56-62.
45. Qi P, Volkin DB, Zhao H, Nedved ML, Hughes R, Bass R, et al. Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci. 2009;98:3117-30.
46. Liu H, Gaza-Bulseco G, Zhou L. Mass spectrometry analysis of photo-induced methionine oxidation of a recombinant human monoclonal antibody. J Am Soc Mass Spectrom. 2009;20:525-8.
47. Rao PE, Kroon DJ. Orthoclone OKT3. Chemical mechanisms and functional effects of degradation of a therapeutic monoclonal antibody. Pharm Biotechnol. 1993;5:135-58.
48. Lam XM, Yang JY, Cleland JL. Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci. 1997;86:1250-5.
49. Gaza-Bulseco G, Faldu S, Hurkmans K, Chumsae C, Liu H. 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. 2008;870:55-62.
50. Bertolotti-Ciarlet A, Wang WR, Lownes R, Pristatsky P, Fang YL, McKelvey T, et al. Impact of methionine oxidation on the binding of human IgG1 to FcRn and Fc gamma receptors. Mol Immunol. 2009;46:1878-82.
51. Wang W, Vlasak J, Li Y, Pristatsky P, Fang Y, Pittman T, Roman J, Wang Y, Prueksaritanont T, Ionescu R. Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol. 2011;48:860-66.
52. Liu D, Ren D, Huang H, Dankberg J, Rosenfeld R, Cocco MJ, et al. Structure and stability changes of human IgG1 Fc as a consequence of methionine oxidation. Biochemistry. 2008;47:5088-100.
53. Wang S, Ionescu R, Peekhaus N, Leung JY, Ha S, Vlasak J. Separation of post-translational modifications in monoclonal antibodies by exploiting subtle conformational changes under mildly acidic conditions. J Chromatogr A. 2010;1217:6496-502.
54. Liu H, Gaza-Bulseco G, Xiang T, Chumsae C. Structural effect of deglycosylation and methionine oxidation on a recombinant monoclonal antibody. Mol Immunol. 2008;45:701-8.
55. 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.
56. Houde D, Peng Y, Berkowitz SA, Engen JR. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Mol Cell Proteomics. 2010;9:1716-28.
57. Filipe V, Jiskoot W, Basmeleh AH, Halim A, Schellekens H, Brinks V. Immunogenicity of different stressed IgG monoclonal antibody formulations in immune tolerant transgenic mice. MAbs. 2012;4:740-52.
58. Brinks V, Jiskoot W, Schellekens H. Immunogenicity of Therapeutic Proteins: The Use of Animal Models. Pharm Res. 2011;28:2379-85.
59. Johnson R, Jiskoot W. Models for evaluation of relative immunogenic potential of protein particles in biopharmaceutical protein formulations. J Pharm Sci. 2012;101:3586-92.
60. Brinks V, Weinbuch D, Baker M, Dean Y, Stas P, Kostense S, et al. Preclinical models used for immunogenicity prediction of therapeutic proteins. Pharm Res. 2013;30:1719-28.
61. Luo Q, Joubert MK, Stevenson R, Ketchem RR, Narhi LO, Wypych J. Chemical modifications in therapeutic protein aggregates generated under different stress conditions. J Biol Chem. 2011;286:25134-44.
62. Joubert MK, Luo Q, Nashed-Samuel Y, Wypych J, Narhi LO. Classification and characterization of therapeutic antibody aggregates. J Biol Chem. 2011;286:25118-33.
63. Chaderjian WB, Chin ET, Harris RJ, Etcheverry TM. Effect of copper sulfate on performance of a serum-free CHO cell culture process and the level of free thiol in the recombinant antibody expressed. Biotechnol Prog. 2005;21:550-3.
64. Hensel M, Steurer R, Fichtl J, Elger C, Wedekind F, Petzold A, Schlothauer T, Molhoj M, Reusch D, Bulau P. Identification of potential sites for tryptophan oxidation in recombinant antibodies using tert-butylhydroperoxide and quantitative LC-MS. PLoS One. 2011;6:e17708.
65. Wei ZP, Feng JH, Lin HY, Mullapudi S, Bishop E, Tous GI, et al. Identification of a single tryptophan residue as critical for binding activity in a humanized monoclonal antibody against respiratory syncytial virus. Anal Chem. 2007;79:2797-805.
66. Goetze AM, Liu YD, Arroll T, Chu L, Flynn GC. Rates and impact of human antibody glycation in vivo. Glycobiology. 2012;22:221-34.
67. Gaudiano MC, Diociaiuti M, Bertocchi P, Valvo L. Effects induced by hydroxyl radicals on salmon calcitonin: a RP-HPLC, CD and TEM study. Biochim Biophys Acta. 2003;1623:33-40.
68. Tobler PH, Tschopp FA, Dambacher MA, Born W, Fischer JA. Identification and characterization of calcitonin forms in plasma and urine of normal subjects and medullary carcinoma patients. J Clin Endocrinol Metab. 1983;57:749-54.
69. Neher R, Riniker B, Maier R, Byfield PG, Gudmundsson TV, MacIntyre I. Human calcitonin. Nature. 1968;220:984-6.
70. Riniker B, Neher R, Maier R, Kahnt FW, Byfield PG, Gudmundsson TV, et al. Human calcitonin. I. Isolation and characterization. Helv Chim Acta. 1968;51:1738-42.
71. Mulinacci F, Poirier E, Capelle MA, Gurny R, Arvinte T. Enhanced physical stability of human calcitonin after methionine oxidation. Eur J Pharm Biopharm 2011;78:229-38.
72. Gaudiano MC, Colone M, Bombelli C, Chistolini P, Valvo L, Diociaiuti M. Early stages of salmon calcitonin aggregation: Effect induced by ageing and oxidation processes in water and in the presence of model membranes. Biochimica Et Biophysica Acta-Proteins and Proteomics. 2005;1750:134-45.
73. Windisch V, DeLuccia F, Duhau L, Herman F, Mencel JJ, Tang SY, et al. Degradation pathways of salmon calcitonin in aqueous solution. J Pharm Sci. 1997;86:359-64.
74. Reubsaet JL, Beijnen JH, Bult A, Hop E, Scholten SD, Teeuwsen J, et al. Oxidation of recombinant methionyl human granulocyte colony stimulating factor. J Pharm Biomed Anal. 1998;17:283-9.
75. Lu HS, Fausset PR, Narhi LO, Horan T, Shinagawa K, Shimamoto G, et al. Chemical modification and site-directed mutagenesis of methionine residues in recombinant human granulocyte colony-stimulating factor: Effect on stability and biological activity. Arch Biochem Biophys. 1999;362:1-11.
76. Arakawa T, Prestrelski SJ, Narhi LO, Boone TC, Kenney WC. Cysteine 17 of recombinant human granulocyte-colony stimulating factor is partially solvent-exposed. J Protein Chem. 1993;12:525-31.
77. Raso SW, Abel J, Barnes JM, Maloney KM, Pipes G, Treuheit MJ, et al. Aggregation of granulocyte-colony stimulating factor in vitro involves a conformationally altered monomeric state. Protein Sci. 2005;14:2246-57.
78. Mulinacci F, Bell SEJ, Capelle MAH, Gurny R, Arvinte T. Oxidized recombinant human growth hormone that maintains conformational integrity. J Pharm Sci. 2011;100:110-22.
79. Teh LC, Murphy LJ, Huq NL, Surus AS, Friesen HG, Lazarus L, et al. Methionine oxidation in human growth hormone and human chorionic somatomammotropin. Effects on receptor binding and biological activities. J Biol Chem. 1987;262:6472-7.
80. Mulinacci F, Capelle MA, Gurny R, Drake AF, Arvinte T. Stability of human growth hormone: influence of methionine oxidation on thermal folding. J Pharm Sci. 2011;100:451-463.
81. Cunningham BC, Wells JA. Comparison of a structural and a functional epitope. J Mol Biol. 1993;234:554-63.
82. de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992;255:306-12.
83. Hepner F, Cszasar E, Roitinger E, Lubec G. Mass spectrometrical analysis of recombinant human growth hormone (Genotropin(R)) reveals amino acid substitutions in 2% of the expressed protein. Proteome Sci. 2005;3:1.
84. D. Steinmann, J. A. Ji, Y. J. Wang, C. Schöneich. Oxidation of human growth hormone by oxygen-centered radicals: formation of Leu-101 hydroperoxide and Tyr-103 oxidation products. Mol Pharm. 9:803-814.
85. Chang SH, Teshima GM, Milby T, GilleceCastro B, CanovaDavis E. Metal-catalyzed photooxidation of histidine in human growth hormone. Anal Biochem. 1997;244:221-7.
86. Hovorka SW, Hong J, Cleland JL, Schöneich C. Metal-catalyzed oxidation of human growth hormone: modulation by solvent-induced changes of protein conformation. J Pharm Sci. 2001;90:58-69.
87. Zhao F, Ghezzo-Schöneich E, Aced GI, Hong J, Milby T, Schöneich C. Metal-catalyzed oxidation of histidine in human growth hormone. Mechanism, isotope effects, and inhibition by a mild denaturing alcohol. J Biol Chem. 1997;272:9019-29.
88. Sanger F. Fractionation of oxidized insulin. Biochem J. 1949;44:126-8.
89. Costantino HR, Langer R, Klibanov AM. Moisture-Induced Aggregation of Lyophilized Insulin. Pharm Res. 1994;11:21-9.
90. Torosantucci R, Weinbuch D, Klem R, Jiskoot W. Triethylenetetramine prevents insulin aggregation and fragmentation during copper catalyzed oxidation. Eur J Pharm Biopharm. 2013;84:464-71.
91. Hovorka SW, Biesiada H, Williams TD, Huhmer A, Schöneich C. High sensitivity of Zn2+ insulin to metal-catalyzed oxidation: detection of 2-oxo-histidine by tandem mass spectrometry. Pharm Res. 2002;19:530-7.
92. Sadineni V, Schöneich C. Selective oxidation of Zn2+ - Insulin catalyzed by Cu2+. J Pharm Sci. 2007;96:1844-7.
93. Tantipolphan R, Romeijn S, den Engelsman J, Torosantucci R, Rasmussen T, Jiskoot W. Elution behavior of insulin on high-performance size exclusion chromatography at neutral pH. J Pharm Biomed Anal. 2010;52:195-202.
94. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res. 2012;29:2104-14.
95. Maritim AC, Sanders RA, Watkins 3rd JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17:24-38.
96. Hunter SJ, Boyd AC, O'Harte FP, McKillop AM, Wiggam MI, Mooney MH, et al. Demonstration of glycated insulin in human diabetic plasma and decreased biological activity assessed by euglycemic-hyperinsulinemic clamp technique in humans. Diabetes. 2003;52:492-8.
97. Thornalley PJ, Langborg A, Minhas HS. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J. 1999;344(Pt 1):109-16.
98. Jia X, Olson DJ, Ross AR, Wu L. Structural and functional changes in human insulin induced by methylglyoxal. FASEB J. 2006;20:1555-7.
99. Pillon NJ, Vella RE, Souleere L, Becchi M, Lagarde M, Soulage CO. Structural and functional changes in human insulin induced by the lipid peroxidation byproducts 4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal. Chem Res Toxicol. 2011;24:752-62.
100. 2+. Eur J Biochem. 1994;223:759-64.
101. Guedes S, Vitorino R, Domingues MRM, Amado F, Domingues P. Oxidative modifications in glycated insulin. Anal Bioanal Chem. 2010;397:1985-95.
102. Gliemann J, Gammeltoft S. The biological activity and the binding affinity of modified insulins determined on isolated rat fat cells. Diabetologia. 1974;10:105-13.
103. Montes-Cortes DH, Hicks JJ, Ceballos-Reyes GM, Garcia-Sanchez JR, Medina-Navarro R, Olivares-Corichi IM. Chemical and functional changes of human insulin by in vitro incubation with blood from diabetic patients in oxidative stress. Metabolism. 2010;59:935-42.
104. Olivares-Corichi IM, Ceballos G, Medina-Santillan R, Medina-Navarro R, Guzman-Grenfell AM, Hicks JJ. Oxidation by reactive oxygen species (ROS) alters the structure of human insulin and decreases the insulin-dependent D-glucose-C14 utilization by human adipose tissue. Front Biosci. 2005;10:3127-31.
105. Sharma VK, Kalonia DS. Polyethylene glycol-induced precipitation of interferon alpha-2a followed by vacuum drying: development of a novel process for obtaining a dry, stable powder. AAPS PharmSci. 2004;6:E4.
106. Larocque L, Bliu A, Xu R, Diress A, Wang J, Lin R, et al. Bioactivity determination of native and variant forms of therapeutic interferons. J Biomed Biotechnol. 2011;2011:174615.
107. Ryff JC. Clinical investigation of the immunogenicity of interferon-alpha 2a. J Interferon Cytokine Res. 1997;17 Suppl 1:S29-33.
108. Hochuli E. Interferon immunogenicity: technical evaluation of interferon-alpha 2a. J Interferon Cytokine Res. 1997;17 Suppl 1:S15-21.
109. Cindric M, Galic N, Vuletic M, Klaric M, Drevenkar V. Evaluation of recombinant human interferon alpha-2b structure and stability by in-gel tryptic digestion, H/D exchange and mass spectrometry. J Pharm Biomed Anal. 2006;40:781-7.
110. Praveen GL, Kumar RB, Shen J, Gaspar K, Docherty J, Foldvari M. Stabilization of Interferon alpha-2b in a Topical Cream. Pharm Technol. 2009;33:80-6.
111. Gitlin G, Tsarbopoulos A, Patel ST, Sydor W, Pramanik BN, Jacobs S, et al. Isolation and characterization of a monomethioninesulfoxide variant of interferon alpha-2b. Pharm Res. 1996;13:762-9.
112. Hermeling S, Aranha L, Damen JMA, Slijper M, Schellekens H, Crommelin DJA, et al. Structural characterization and immunogenicity in wild-type and immune tolerant mice of degraded recombinant human interferon alpha2b. Pharm Res. 2005;22:1997-2006.
113. Davis ME, Maxwell CV, Brown DC, de Rodas BZ, Johnson ZB, Kegley EB, et al. Effect of dietary mannan oligosaccharides and(or) pharmacological additions of copper sulfate on growth performance and immunocompetence of weanling and growing/finishing pigs. J Anim Sci. 2002;80:2887-94.
114. Karpusas M, Nolte M, Benton CB, Meier W, Lipscomb WN, Goelz S. The crystal structure of human interferon beta at 2.2-angstrom resolution. Proc Natl Acad Sci USA. 1997;94:11813-8.
115. Mark DF, Lu SD, Creasey AA, Yamamoto R, Lin LS. Site-specific mutagenesis of the human fibroblast interferon gene. Proc Natl Acad Sci USA. 1984;81:5662-6.
116. Runkel L, Meier W, Pepinsky RB, Karpusas M, Whitty A, Kimball K, et al. Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-beta (IFN-beta). Pharm Res. 1998;15:641-9.
117. van Beers MM, Sauerborn M, Gilli F, Brinks V, Schellekens H, Jiskoot W. Oxidized and aggregated recombinant human interferon beta is immunogenic in human interferon beta transgenic mice. Pharm Res. 2011;28:2393-402.
118. Torosantucci R, Sharov VS, van Beers M, Brinks V, Schöneich C, Jiskoot W. Identification of oxidation sites and covalent cross-links in metal catalyzed oxidized interferon beta-1a: potential implications for protein aggregation and immunogenicity. Mol Pharm. 2013;10:2311-22.
119. Avanti C, Amorij JP, Setyaningsih D, Hawe A, Jiskoot W, Visser J, et al. A new strategy to stabilize oxytocin in aqueous solutions: I. The effects of divalent metal ions and citrate buffer. AAPS Journal. 2011;13:284-90.
120. Hawe A, Poole R, Romeijn S, Kasper P, van der Heijden R, Jiskoot W. Towards heat-stable oxytocin formulations: analysis of degradation kinetics and identification of degradation products. Pharm Res. 2009;26:1679-88.
121. Rosei RCMA, Blarzino C, Foppoli C, Mosca L. The oxidation of oxytocin and vasopressin by peroxidase/H2O2 system. Amino Acids. 1995;8:385-91.
122. Kato Y, Kitamoto N, Kawai Y, Osawa T. The hydrogen peroxide/copper ion system, but not other metal-catalyzed oxidation systems, produces protein-bound dityrosine. Free Radic Biol Med. 2001;31:624-32.
123. Hocher B, Armbruster FP, Stoeva S, Reichetzeder C, Gron HJ, Lieker I, Khadzhynov D, Slowinski T, Roth HJ. Measuring parathyroid hormone (PTH) in patients with oxidative stress - do we need a fourth generation parathyroid hormone assay? PLoS One. 2012;7:e40242.
124. Kamberi M, Kim YJ, Jun B, Riley CM. The effects of sucrose on stability of human brain natriuretic peptide [hBNP (1-32)] and human parathyroid hormone [hPTH (1-34)]. J Pept Res. 2005;66:348-56.
125. Barden JA, Kemp BE. NMR solution structure of human parathyroid hormone(1-34). Biochemistry. 1993;32:7126-32.
126. Zull JE, Smith SK, Wiltshire R. Effect of methionine oxidation and deletion of amino-terminal residues on the conformation of parathyroid hormone. Circular dichroism studies. J Biol Chem. 1990;265:5671-6.
127. Nabuchi Y, Fujiwara E, Ueno K, Kuboniwa H, Asoh Y, Ushio H. Oxidation of recombinant human parathyroid hormone: Effect of oxidized position on the biological activity. Pharm Res. 1995;12:2049-52.
128. Mozziconacci O, Ji JA, Wang YJ, Schöneich C. Metal-catalyzed oxidation of protein methionine residues in human parathyroid hormone (1-34): formation of homocysteine and a novel methionine-dependent hydrolysis reaction. Mol Pharm. 2013;10:739-55.
129. Frelinger 3rd AL, Zull JE. Oxidized forms of parathyroid hormone with biological activity. Separation and characterization of hormone forms oxidized at methionine 8 and methionine 18. J Biol Chem. 1984;259:5507-13.
130. Woodhead JS, O'Riordan JL, Keutmann HT, Stoltz ML, Dawson BF, Niall HD, et al. Isolation and chemical properties of porcine parathyroid hormone. Biochemistry. 1971;10:2787-92.
131. Caulfield MP, McKee RL, Goldman ME, Duong LT, Fisher JE, Gay CT, et al. The bovine renal parathyroid hormone (PTH) receptor has equal affinity for two different amino acid sequences: the receptor binding domains of PTH and PTH-related protein are located within the 14-34 region. Endocrinology. 1990;127:83-7.
132. Frelinger 3rd AL, Zull JE. The role of the methionine residues in the structure and function of parathyroid hormone. Arch Biochem Biophys. 1986;244:641-9.