The photolysis of disulfide bonds in IgG1 and IgG2 leads to selective intramolecular hydrogen transfer reactions of cysteine thiyl radicals, probed by covalent H/D exchange and RPLC-MS/MS analysis

Pharmaceutical Research

Volumn 30, Issue 5, 2013, Pages 1291-1299

  Zhou, Shuxia ^a   Mozziconacci, Olivier ^a   Kerwin, Bruce A ^b   Schöneich, Christian ^a  

^a UNIVERSITY OF KANSAS   (United States)

^b AMGEN INC   (United States)

Author keywords

carbon centered radical; covalent hydrogen deuterium (H D) exchange; cysteine thiyl radical (CysS ); intramolecular hydrogen transfer; photo degradation

Indexed keywords

CYSTEINE DERIVATIVE; CYSTEINE THIYL RADICAL; DEUTERIUM; HYDROGEN; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; VALYLTHREONYLVALYLLEUCYLGLYCYLGLUTAMINYLPROLYLLYSINE; VALYLVALYLSERYLVALYLLEUCYLTHREONYLVALYLVALYLHISTIDINYLGLUTAMINYLASPARTYLTRYPTOPHYLLEUCYLASPARAGINYLGLYCYLLYSINE;

AMINO ACID SEQUENCE; ARTICLE; CONTROLLED STUDY; COVALENT BOND; DISULFIDE BOND; MASS SPECTROMETRY; PHOTOLYSIS; PRIORITY JOURNAL; REVERSED PHASE LIQUID CHROMATOGRAPHY; ULTRAVIOLET RADIATION; VALIDATION STUDY;

AMINO ACID SEQUENCE; CYSTEINE; DEUTERIUM EXCHANGE MEASUREMENT; DISULFIDES; HYDROGEN; IMMUNOGLOBULIN G; MOLECULAR SEQUENCE DATA; PEPTIDES; PHOTOLYSIS; TANDEM MASS SPECTROMETRY; ULTRAVIOLET RAYS;

EID: 84876458314     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-012-0968-1     Document Type: Article

References (23)

1. Brekke OH, Sandlie I. Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat Rev Drug Discov. 2003;2:52-62.
2. Bebbington C, Yarranton G. Antibodies for the treatment of bacterial infections: current experience and future prospects. Curr Opin Biotechnol. 2008;19:613-9.
3. Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov. 2006;5:147-59.
4. Volkin DB, Mach H, Middaugh CR. Degradative covalent reactions important to protein stability. Mol Biotechnol. 1997;8:105-22.
5. ICH harmonised tripartite guideline: guideline for the photostability testing of new drug substances and products. J Postgrad Med. 2001;47:264.
6. Ellison D, Stalteri MA, Mather SJ. Photoreduction of monoclonal antibodies for conjugation and fragmentation. Biotechniques. 2000;28:318-22. 324-316.
7. Lam XM, Yang JY, Cleland JL. Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci. 1997;86:1250-5.
8. Bonifačić M, Asmus KD. Free radical oxidation of organic disulfides. J Phys Chem. 1976;80:2426-30.
9. Bonifačić M, Asmus KD. Radical reactions in aqueous disulphide-thiol systems. Int J Radiat Biol Re. 1984;46:35-45.
10. Bonifačić M, Schaefer K, Moeckel H, Asmus KD. Primary steps in the reactions of organic disulfides with hydroxyl radicals in aqueous solution. J Phys Chem. 1975;79:1496-502.
11. Creed D. The photophysics and photochemistry of the near-UV absorbing amino acids. Photochem Photobiol. 1984;39:577-83.
12. Everett SA, Schöneich C, Stewart JH, Asmus KD. Perthiyl radicals, trisulfide radical ions, and sulfate formation: a combined photolysis and radiolysis study on redox processes with organic di- and trisulfides. J Phys Chem. 1992;96:306-14.
13. 2S, and hydrogen transfer reactions. J Phys Chem B. 2010;114:3668-88.
14. Mozziconacci O, Kerwin BA, Schöneich C. Exposure of a monoclonal antibody, IgG1, to UV-light leads to protein dithiohemiacetal and thioether cross-links: A role for thiyl radicals. Chem Res Toxicol. 2010;23:1310-2.
15. Mozziconacci O, Kerwin BA, Schöneich C. 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. 2010;114:6751-62.
16. Mozziconacci O, Sharov V, Williams TD, Kerwin BA, Schöneich C. Peptide cysteine thiyl radicals abstract hydrogen atoms from surrounding amino acids: the photolysis of a cystine containing model peptide. J Phys Chem B. 2008;112:9250-7.
17. Mozziconacci O, Williams TD, Kerwin BA, Schöneich C. Reversible intramolecular hydrogen transfer between protein cysteine thiyl radicals and alpha C-H bonds in insulin: control of selectivity by secondary structure. J Phys Chem B. 2008;112:15921-32.
18. Lorenz CM, Wolk BM, Quan CP, Alcala EW, Eng M, McDonald DJ, et al. The effect of low intensity ultraviolet-C light on monoclonal antibodies. Biotechnol Prog. 2009;25:476-82.
19. Male D, Brostoff J, Roth DB, Roitt I. Immunology. Mosby: Elsevier; 2006.
20. Rauk A, Armstrong DA. Influence of beta-sheet structure on the susceptibility of proteins to backbone oxidative damage: preference for C(alpha)-centered radical formation at glycine residues of antiparallel beta-sheets. J Am Chem Soc. 2000;122:4185-92.
21. Rauk A, Yu D, Armstrong DA. Oxidative damage to and by cysteine in proteins: an ab initio study of the radical structures, C-H, S-H, and C-C bond dissociation energies, and transition structures for H abstraction by thiyl radicals. J Am Chem Soc. 1998;120:8848-55.
22. Mason BD, Schoneich C, Kerwin BA. Effect of pH and light on aggregation and conformation of an IgG1 mAb. Mol Pharm. 2012;9:774-90.
23. 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.