靶向拯救癌症相关 IDH1 突变活性的工程合成抗体。

Department of Chemistry and Biochemistry, Indiana University South Bend, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana, USA.

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.

Sci Rep. 2017 Apr 3;7(1):556. doi: 10.1038/s41598-017-00728-1.

We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with brain tumors. The results show that this strategy is a first step towards developing "activator drugs" for a large number of genetic disorders where mutations have disrupted protein function.

我们利用了一个高多样性的噬菌体展示文库来设计能够调节异柠檬酸脱氢酶 1（IDH1）活性的抗体片段（Fabs）。我们表明，一种构象特异性 Fab 可以使与脑肿瘤相关的 IDH1 突变体重新激活。结果表明，这种策略是朝着开发“激活药物”迈出的第一步，这些药物针对的是许多遗传疾病，这些疾病的突变破坏了蛋白质的功能。