Peptide-Directed Photo-Cross-Linking for Site-Specific Conjugation of IgG,Bioconjugate Chemistry

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Peptide-Directed Photo-Cross-Linking for Site-Specific Conjugation of IgG
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-09-04 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00515
Jisoo Park , Yumi Lee , Byoung Joon Ko ₁ , Tae Hyeon Yoo

Affiliation

Conjugation of antibody has expanded its applications in therapeutics and diagnostics, and various methods have been developed based on chemical or enzymatic reactions. However, the majority of them have focused on synthetic molecules such as small molecules, nucleic acids, or synthetic materials, but site-specific conjugation of antibody with protein cargo has rarely been demonstrated. In this Communication, we report a PEptide-DIrected Photo-cross-linking (PEDIP) reaction for site-specific conjugation of IgG with protein using an Fc-binding peptide and a photoreactive amino acid analogue, and demonstrate this method by developing an immunotoxin composed of a Her2-targeting IgG (trastuzumab) and an engineered Pseudomonas exotoxin A (PE24). The ADP-ribosylation of eukaryotic elongation factor-2 by the bacterial toxin inhibits the ribosomal translation of protein, and the trastuzumab-PE24 conjugate exhibited the cytotoxicity toward Her2-overexpressing cell lines. The PEDIP reaction can also be applied for many other types of cargo with slight modifications of the method.

中文翻译：

用于 IgG 位点特异性缀合的肽定向光交联

抗体的缀合扩大了其在治疗和诊断中的应用，并且基于化学或酶反应开发了各种方法。然而，他们中的大多数都集中在合成分子，如小分子、核酸或合成材料，但抗体与蛋白质货物的位点特异性缀合很少被证明。在本通讯中，我们报告了使用 Fc 结合肽和光反应性氨基酸类似物进行 IgG 与蛋白质位点特异性缀合的 PE 肽定向光交联 (PEDIP) 反应，并通过开发由Her2 靶向 IgG（曲妥珠单抗）和工程假单胞菌外毒素 A (PE24)。细菌毒素对真核延伸因子-2 的 ADP 核糖基化抑制蛋白质的核糖体翻译，曲妥珠单抗-PE24 缀合物对 Her2 过表达细胞系表现出细胞毒性。 PEDIP 反应也可应用于许多其他类型的货物，只需稍微修改方法即可。

更新日期：2018-09-04

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