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Small-Molecule Probes for Affinity-Guided Introduction of Biocompatible Handles on Metal-Binding Proteins
Bioconjugate Chemistry ( IF 4.7 ) Pub Date : 2018-08-09 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00424
Michael R. Mortensen 1, 2 , Mikkel B. Skovsgaard 1, 2 , Anders H. Okholm 1 , Carsten Scavenius 3 , Daniel M. Dupont 1 , Christian B. Rosen 1, 2 , Jan J. Enghild 3 , Jørgen Kjems 1 , Kurt V. Gothelf 1, 2
Affiliation  

Protein conjugates of high heterogeneity may contain species with significantly different biological properties, and as a consequence, the focus on methods for production of conjugates of higher quality has increased. Here, we demonstrate an efficient and generic approach for the modification of metal-binding proteins with biocompatible chemical handles without the need for genetic modifications. Affinity-guided small-molecule probes are developed for direct conjugation to off-the-shelf proteins and for installing different chemical handles on the protein surface. While purification of protein conjugates obtained by small molecule conjugation is troublesome, the affinity motifs of the probes presented here allow for purification of the conjugates. The versatility of the probes is demonstrated by conjugation to several His-tagged and natural metal-binding proteins, including the efficient and area-selective conjugation to three therapeutically relevant antibodies.

中文翻译:

亲和引导的金属结合蛋白生物相容性手柄的小分子探针。

高异质性的蛋白质缀合物可能包含具有明显不同的生物学特性的物种,因此,对生产更高质量的缀合物的方法的关注增加了。在这里,我们演示了一种有效且通用的方法,可通过生物相容性化学修饰来修饰金属结合蛋白,而无需进行基因修饰。亲和引导的小分子探针被开发用于直接与现成的蛋白质结合,并在蛋白质表面上安装不同的化学手柄。虽然通过小分子偶联获得的蛋白质偶联物的纯化很麻烦,但此处介绍的探针的亲和性基序可用于偶联物的纯化。
更新日期:2018-08-09
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