Exposure of a monoclonal antibody, IgG1, to UV-light leads to protein dithiohemiacetal and thioether cross-links: a role for thiyl radicals?
Recently, we characterized a thiyl radical-dependent mechanism for the photolytic conversion of a disulfide bond in a model peptide into dithiohemiacetal and subsequently into thioether ( Mozziconacci et al. ( 2010 ) J. Phys. Chem B 114 , 3668 - 3688 ). This mechanism is of potential relevance for the photodegradation of disulfide-containing proteins, which may be a problem for the production and formulation of diagnostic and therapeutic protein pharmaceuticals. In this Rapid Report, we show that similar products are also formed when an antibody (IgG1) is subjected to photoirradiation at 253.7 nm, suggesting the involvement of thiyl radicals also in these processes. A series of dithiohemiacetal and thioether cross-links were identified in photoirradiated IgG1 through HPLC-MS/MS analysis.
Mozziconacci
Olivier
O
Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, KS 66047, USA.
Kerwin
Bruce A
BA
Schöneich
Christian
C
D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals / Q000737:chemistry / Q000528:radiation effects; D007074:Immunoglobulin G / Q000737:chemistry*; D010777:Photochemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000528:radiation effects*; D013440:Sulfides / Q000737:chemistry / Q000528:radiation effects*; D053719:Tandem Mass Spectrometry; D014466:Ultraviolet Rays
D005609:Free Radicals; D007074:Immunoglobulin G; D013438:Sulfhydryl Compounds; D013440:Sulfides