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.

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。