A new algorithm to convert a normal antibody into the corresponding catalytic antibody

摘要

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 Prosup95/sup, a highly conserved residue in CDR-3 of the antibody light chain. The deletion of Prosup95/sup is a key contributor to catalytic function of the light chain. The S35 and S38 light chains have identical amino acid sequences except for Prosup95/sup. The former, with Prosup95/sup did not show any catalytic activity, whereas the latter, without Prosup95/sup, exhibited peptidase activity. To verify the generality of this finding, we tested another light chain, T99wt, which had Prosup95/sup and showed little catalytic activity. In contrast, a Prosup95/sup-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.