Homogeneous bispecifics by disulfide bridging.

Homogeneous bispecifics by disulfide bridging.
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DOI:
10.1021/bc5002467
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发表时间:
2014-08-20
影响因子:
4.7
通讯作者:
Baker, James R.
Baker, James R.
中科院分区:
化学2区
文献类型:
--
作者:
Hull, Elizabeth A.;Livanos, Maria;Miranda, Enrique;Smith, Mark E. B.;Chester, Kerry A.;Baker, James R.

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我们报告了一种化学平台,通过靶向和桥接二硫键来产生位点特异性,均匀的抗体-抗体偶联物。利用一种容易合成的双溴代亚胺交联剂,通过简单地还原和桥接抗体片段二硫键,获得了一种双特异性抗体结构。维持抗体的结合活性,并观察到与靶抗原的体外结合。该技术通过连接scFv和Fab抗体片段得到了证明,显示了其构建多种双特异性的潜力。
We report on a chemical platform to generate site-specific, homogeneous, antibody–antibody conjugates by targeting and bridging disulfide bonds. A bispecific antibody construct was produced in good yield through simple reduction and bridging of antibody fragment disulfide bonds, using a readily synthesized bis-dibromomaleimide cross-linker. Binding activity of antibodies was maintained, and in vitro binding of target antigens was observed. This technology is demonstrated through linking scFv and Fab antibody fragments, showing its potential for the construction of a diverse range of bispecifics.
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