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A new algorithm to convert a normal antibody into the corresponding catalytic antibody
Science Advances ( IF 11.7 ) Pub Date : 2020-03-25 , DOI: 10.1126/sciadv.aay6441
Emi Hifumi 1 , Hiroaki Taguchi 2 , Haruna Tsuda 1, 3 , Tetsuro Minagawa 1, 3 , Tamami Nonaka 1 , Taizo Uda 1, 4
Affiliation  

Over thousands of monoclonal antibodies (mAbs) have been produced so far, and it would be valuable if these mAbs could be directly converted into catalytic antibodies. We have designed a system to realize the above concept by deleting Pro95, a highly conserved residue in CDR-3 of the antibody light chain. The deletion of Pro95 is a key contributor to catalytic function of the light chain. The S35 and S38 light chains have identical amino acid sequences except for Pro95. The former, with Pro95 did not show any catalytic activity, whereas the latter, without Pro95, exhibited peptidase activity. To verify the generality of this finding, we tested another light chain, T99wt, which had Pro95 and showed little catalytic activity. In contrast, a Pro95-deleted mutant enzymatically degraded the peptide substrate and amyloid-beta molecule. These two cases demonstrate the potential for a new method of creating catalytic antibodies from the corresponding mAbs.



中文翻译:

将普通抗体转化为相应催化抗体的新算法

迄今为止,已经产生了数千种单克隆抗体(mAb),如果这些mAb可以直接转化为催化抗体,那将很有价值。我们设计了一种系统,通过删除Pro 95(一种抗体轻链CDR-3中的高度保守残基)来实现上述概念。Pro 95的缺失是轻链催化功能的关键因素。除了Pro 95外,S35和S38轻链具有相同的氨基酸序列。具有Pro 95的前者没有显示任何催化活性,而没有Pro 95的后者具有肽酶活性。为了验证这一发现的普遍性,我们测试了另一条轻链T99wt,它具有Pro 95并且几乎没有催化活性。相反,Pro 95缺失的突变体酶促降解了肽底物和淀粉样β分子。这两种情况证明了从相应的单克隆抗体产生催化抗体的新方法的潜力。

更新日期:2020-03-26
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