Metal ion interactions with mAbs: Part 1 pH and conformation modulate copper-mediated site-specific fragmentation of the IgG1 hinge region

mAbs

Volumn 7, Issue 5, 2015, Pages 901-911

  Glover, Zephania Kwong ^a   Basa, Louisette ^a   Moore, Benjamin ^a   Laurence, Jennifer S ^b   Sreedhara, Alavattam ^a  

^a GENENTECH INC   (United States)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

Copper; Fragmentation; Hinge; Histidine; Hydrolysis; Kappa light chain; MAb IgG1; Metal binding

Indexed keywords

COPPER; FREE RADICAL; IMMUNOGLOBULIN G1; MONOCLONAL ANTIBODY; IMMUNOGLOBULIN G; RECOMBINANT PROTEIN;

ANIMAL CELL; ARTICLE; BINDING ASSAY; BIOLOGICAL FUNCTIONS; CONTROLLED STUDY; CRYSTAL STRUCTURE; FRAGMENTATION; HINGE REGION; HYDROLYSIS; MASS SPECTROMETRY; MUTANT; NONHUMAN; OXIDATION; PH; PROTEIN CONFORMATION; PROTEIN DEGRADATION; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SIZE EXCLUSION CHROMATOGRAPHY; AMINO ACID SEQUENCE; CHEMICAL STRUCTURE; CHEMISTRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; METABOLISM; PROTEIN STABILITY;

AMINO ACID SEQUENCE; ANTIBODIES, MONOCLONAL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; COPPER; HUMANS; HYDROLYSIS; IMMUNOGLOBULIN G; MASS SPECTROMETRY; MOLECULAR STRUCTURE; PROTEIN STABILITY; RECOMBINANT PROTEINS;

EID: 84954313372     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2015.1062193     Document Type: Article

References (45)

1. Beck A, Wurch T, Bailly C, Corvaia N. Strategies and challenges for the next generation of therapeutic antibodies. Nat Rev Immunol 2010; 10:345-52; PMID:20414207; http://dx. doi. org/10. 1038/nri2747
2. Liu H, Gaza-Bulseco G, Chumsae C, Newby-Kew A. Characterization of lower molecular weight artifact bands of recombinant monoclonal IgG1 antibodies on non-reducing SDS-PAGE. Biotechnol Lett 2007; 29:1611-22; PMID:17609855; http://dx. doi. org/ 10. 1007/s10529-007-9449-8
3. Martin-Moe S, Lim FJ, Wong RL, Sreedhara A, Sundaram J, Sane SU. A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design. J Pharm Sci 2011; 100:3031-43; PMID:21425164; http://dx. doi. org/10. 1002/jps. 22545
4. Vlasak J, Ionescu R. Fragmentation of monoclonal antibodies. mAbs 2011; 3:253-63; PMID:21487244; http://dx. doi. org/10. 4161/mabs. 3. 3. 15608
5. Padlan EA. Anatomy of the antibody molecule. Mol Immunol 1994; 31:169-217; PMID:8114766; http:// dx. doi. org/10. 1016/0161-5890(94)90001-9
6. Cordoba AJ, Shyong BJ, Breen D, Harris RJ. Nonenzymatic hinge region fragmentation of antibodies in solution. J Chromatogr B Anal Technol Biomed Life Sci 2005; 818:115-21; http://dx. doi. org/10. 1016/j. jchromb. 2004. 12. 033
7. Cohen SL, Price C, Vlasak J. Beta-elimination and peptide bond hydrolysis: two distinct mechanisms of human IgG1 hinge fragmentation upon storage. J Am Chem Soc 2007; 129:6976-7; PMID:17500521; http://dx. doi. org/10. 1021/ja0705994
8. 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 U S A 1969; 63:78-85; PMID:5257969; http://dx. doi. org/10. 1073/pnas. 63. 1. 78
9. Wang AC, Wang IY. Cleavage sites of human IgG1 immunoglobulin by papain. Immunochemistry 1977; 14:197-200; PMID:863464; http://dx. doi. org/ 10. 1016/0019-2791(77)90194-X
10. Fan X, Brezski RJ, Fa M, Deng H, Oberholtzer A, Gonzalez A, Dubinsky WP, Strohl WR, Jordan RE, Zhang N, et al. A single proteolytic cleavage within the lower hinge of trastuzumab reduces immune effector function and in vivo efficacy. Breast Cancer Res 2012; 14:R116; PMID:22873525; http://dx. doi. org/ 10. 1186/bcr3240
11. Siepen JA, Keevil EJ, Knight D, Hubbard SJ. Prediction of missed cleavage sites in tryptic peptides aids protein identification in proteomics. J Proteome Res 2007; 6:399-408; PMID:17203985; http://dx. doi. org/ 10. 1021/pr060507u
12. Yan B, Boyd D. Breaking the light and heavy chain linkage of human immunoglobulin G1 (IgG1) by radical reactions. J Biol Chem 2011; 286:24674-84; PMID:21606498; http://dx. doi. org/10. 1074/jbc. M111. 255026
13. Kowalik-Jankowska T, Ruta M, Wisniewska K, Lankiewicz L, Dyba M. Products of Cu(II)-catalyzed oxidation in the presence of hydrogen peroxide of the 1-10, 1-16 fragments of human and mouse beta-amyloid peptide. J Inorg Biochem 2004; 98:940-50; PMID:15149800; http://dx. doi. org/10. 1016/j. jinorgbio. 2004. 03. 001
14. Gaza-Bulseco G, Liu H. Fragmentation of a recombinant monoclonal antibody at various pH. Pharm Res 2008; 25:1881-90; PMID:18473123; http://dx. doi. org/10. 1007/s11095-008-9606-3
15. Xiang T, Lundell E, Sun Z, Liu H. Structural effect of a recombinant monoclonal antibody on hinge region peptide bond hydrolysis. J Chromatogr B: Anal Technol Biomed Life Sci 2007; 858:254-62; http://dx. doi. org/10. 1016/j. jchromb. 2007. 08. 043
16. Yates Z, Gunasekaran K, Zhou H, Hu Z, Liu Z, Ketchem RR, Yan B. Histidine residue mediates radical-induced hinge cleavage of human IgG1. J Biol Chem 2010; 285:18662-71; PMID:20304919; http:// dx. doi. org/10. 1074/jbc. M110. 108597
17. Smith RM, Hansen DE. The pH-rate profile for the hydrolysis of a peptide bond. J Am Chem Soc 1998; 120:8910-3; http://dx. doi. org/10. 1021/ja9804565
18. Radzicka A, Wolfenden R. Rates of uncatalyzed peptide bond hydrolysis in neutral solution and the transition state affinities of proteases. J Am Chem Soc 1996; 118:6105-9; http://dx. doi. org/10. 1021/ja954077c
19. Yashiro M, Sonobe Y, Yamamura A, Takarada T, Komiyama M, Fujii Y. Metal-ion-assisted hydrolysis of dipeptides involving a serine residue in a neutral aqueous solution. Org Biomol Chem 2003; 1:629-32; PMID:12929447; http://dx. doi. org/10. 1039/ b209565c
20. Belczyk-Ciesielska A, Zawisza IA, Mital M, Bonna A, Bal W. Sequence-Specific Cu(II)-Dependent Peptide Bond Hydrolysis: Similarities and Differences with the Ni(II)-Dependent Reaction. Inorg Chem 2014; 53:4639-46; PMID:24735221; http://dx. doi. org/ 10. 1021/ic5003176
21. Krezel A, Mylonas M, Kopera E, Bal W. Sequence-specific Ni(II)-dependent peptide bond hydrolysis in a peptide containing threonine and histidine residues. Acta Biochim Pol 2006; 53:721-7; PMID:17117212
22. Protas AM, Bonna A, Kopera E, Bal W. Selective peptide bond hydrolysis of cysteine peptides in the presence of Ni(II) ions. J Inorg Biochem 2011; 105:10-6; PMID:21134597; http://dx. doi. org/10. 1016/j. jinorgbio. 2010. 09. 003
23. Kaminskaia NV, Kostic NM. New selectivity in peptide hydrolysis by metal complexes. platinum(II) complexes promote cleavage of peptides next to the tryptophan residue. Inorg Chem 2001; 40:2368-77; PMID:11327915; http://dx. doi. org/10. 1021/ ic0014033
24. Regan L. The Design of Metal-Binding Sites in Proteins. Annu Rev Biophys Biomol Struct 1993; 22:257-81; PMID:8347991; http://dx. doi. org/10. 1146/ annurev. bb. 22. 060193. 001353
25. Koch KA, Pena MM, Thiele DJ. Copper-binding motifs in catalysis, transport, detoxification and signaling. Chem Biol 1997; 4:549-60; PMID:9281528; http://dx. doi. org/10. 1016/S1074-5521(97)90241-6
26. Katz AK, Shimoni-Livny L, Navon O, Navon N, Bock CW, Glusker JP. Copper-binding motifs: Structural and theoretical aspects. Helv Chim Acta 2003; 86:1320-38; http://dx. doi. org/10. 1002/ hlca. 200390120
27. -2Hydrolyzes Both Dipeptides and Proteins. J Am Chem Soc 1995; 117:7015-6; http://dx. doi. org/10. 1021/ja00131a030
28. 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; PMID:15801797; http://dx. doi. org/ 10. 1021/bp0497029
29. Salinas BA, Sathish HA, Shah AU, Carpenter JF, Randolph TW. Buffer-dependent fragmentation of a humanized full-length monoclonal antibody. J Pharm Sci 2010; 99:2962-74; PMID:20091831; http://dx. doi. org/10. 1002/jps. 21797
30. Smith MA, Easton M, Everett P, Lewis G, Payne M, Riveros-Moreno V, Allen G. Specific cleavage of immunoglobulin G by copper ions. Int J Pept Protein Res 1996; 48:48-55; http://dx. doi. org/10. 1111/j. 1399-3011. 1996. tb01105. x
31. Allen G, Campbell RO. Specific cleavage of histidinecontaining peptides by copper(II). Int J Pept Protein Res 1996; 48:265-73; PMID:8897094; http://dx. doi. org/10. 1111/j. 1399-3011. 1996. tb00840. x
32. Cunningham BC, Wells JA. High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis. Science 1989; 244:1081-5; PMID:2471267; http://dx. doi. org/10. 1126/science. 2471267
33. Kamerzell TJ, Li M, Arora S, Ji JA, Wang YJ. The relative rate of immunoglobulin gamma 1 fragmentation. J Pharm Sci 2011; 100:1341-9; PMID:24081469; http://dx. doi. org/10. 1002/jps. 22389
34. Giles NM, Watts AB, Giles GI, Fry FH, Littlechild JA, Jacob C. Metal and redox modulation of cysteine protein function. Chem Biol 2003; 10:677-93; PMID:12954327; http://dx. doi. org/10. 1016/S1074-5521(03)00174-1
35. Saphire EO, Parren PW, Pantophlet R, Zwick MB, Morris GM, Rudd PM, Dwek RA, Stanfield RL, Burton DR, Wilson IA. Crystal structure of neutralizing humam IGG against HIV-1: a template for vaccine design. Science 2001; 293(5532): 1155-9.
36. Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, et al. Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cellfree hydrogen peroxide production and metal reduction. J Biol Chem 1999; 274:37111-6; PMID:10601271; http://dx. doi. org/10. 1074/ jbc. 274. 52. 37111
37. Schultz J, Allison H, Grice M. Specificity of the cleavage of proteins by dilute acid. I. Release of aspartic acid from insulin, ribonuclease, and glucagon. Biochemistry 1962; 1:694-8; PMID:13909510; http://dx. doi. org/ 10. 1021/bi00910a024
38. Rustandi RR, Wang Y. Use of CE-SDS gel for characterization of monoclonal antibody hinge region clipping due to copper and high pH stress. Electrophoresis 2011; 32:3078-84; PMID:22145164; http://dx. doi. org/10. 1002/elps. 201100186
39. Zhang L, Mei Y, Zhang Y, Li S, Sun X, Zhu L. Regioselective cleavage of myoglobin with copper(II) compounds at neutral pH. Inorg Chem 2003; 42:492-8; PMID:12693231; http://dx. doi. org/10. 1021/ic025619b
40. Bogdanowich-Knipp SJ, Chakrabarti S, Williams TD, Dillman RK, Siahaan TJ. Solution stability of linear vs. cyclic RGD peptides. J Pept Res 1999; 53:530-41; PMID:10424348; http://dx. doi. org/10. 1034/j. 1399-3011. 1999. 00052. x
41. Khossravi M, Borchardt RT. Chemical pathways of peptide degradation: IX. Metal-catalyzed oxidation of histidine in model peptides. Pharm Res 1998; 15:1096-102; PMID:9688066; http://dx. doi. org/ 10. 1023/A:1011946631197
42. Sreedhara A, Lau K, Li C, Hosken B, Macchi F, Zhan D, Shen A, Steinmann D, Schoneich C, Lentz Y. Role of surface exposed tryptophan as substrate generators for the antibody catalyzed water oxidation pathway. Mol Pharmaceutics 2013; 10:278-88; http://dx. doi. org/10. 1021/mp300418r
43. Sankararamakrishnan R, Verma S, Kumar S. ATCUNlike metal-binding motifs in proteins: identification and characterization by crystal structure and sequence analysis. Proteins 2005; 58:211-21; PMID:15508143; http://dx. doi. org/10. 1002/prot. 20265
44. Ouellette D, Alessandri L, Piparia R, Aikhoje A, Chin A, Radziejewski C, Correia I. Elevated cleavage of human immunoglobulin gamma molecules containing a lambda light chain mediated by iron and histidine. Anal Biochem 2009; 389:107-17; PMID:19318085; http://dx. doi. org/10. 1016/j. ab. 2009. 03. 027
45. The PyMOL Molecular Graphics System, Version 1. 5. 0. 5. New York, NY: Schrodinger, LLC. Available at https://www. pymol. org/