Bio-reduction of Redox-Sensitive Albumin Conjugates in FcRn-Expressing Cells

被引:16
作者
Bruelisauer, Lorine [1 ]
Valentino, Gina [1 ]
Morinaga, Sakura [1 ]
Cam, Kuebra [1 ]
Bukrinski, Jens Thostrup [3 ]
Gauthier, Marc A. [2 ]
Leroux, Jean-Christophe [1 ]
机构
[1] Swiss Fed Inst Technol Zurich ETHZ, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland
[2] EMT Res Ctr, INRS, Varennes, PQ J3X 1S2, Canada
[3] Novozymes AS, DK-2880 Bagsvaerd, Denmark
关键词
albumin; disulfide; drug delivery; FcRn receptors; reduction; SURFACE THIOLS; DRUG-DELIVERY; HALF-LIFE; IGG; PHARMACOKINETICS; MECHANISM; RECEPTOR; PROTEIN; DEGRADATION; ANTIBODIES;
D O I
10.1002/anie.201404238
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Disulfide-containing IgG-, Fc-, or albumin-based prodrugs that rely on FcRn-trafficking by endothelial cells for prolonged circulation in the body might be hampered by premature bio-reduction processes during FcRn-mediated recycling events. A detailed bio-reduction analysis of redox-sensitive albumin conjugates in two FcRn-expressing cell lines has been performed. The obtained results indicate that the FcRn-mediated recycling pathway is not (or is only poorly) bio-reducing.
引用
收藏
页码:8392 / 8396
页数:5
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