Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, KS 66047, USA.
Chem Res Toxicol. 2010 Aug 16;23(8):1310-2. doi: 10.1021/tx100193b.
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.
最近，我们描述了一种硫自由基依赖的机制，用于将模型肽中二硫键的光解转化为二硫代半缩醛，随后转化为硫醚（ Mozziconacci 等人（ 2010 ）J. Phys. Chem. B 114,3668-3688）。这种机制对于含二硫键的蛋白质的光降解具有潜在的相关性，这可能是诊断和治疗性蛋白药物生产和配方的一个问题。在这个快速报告中，我们表明，当抗体（IgG1）在 253.7nm 下进行光照射时，也会形成类似的产物，这表明硫自由基也参与了这些过程。通过 HPLC-MS/MS 分析，在光照射的 IgG1 中鉴定出一系列二硫代半缩醛和硫醚交联物。
