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. 2016 Feb 10;270(1):165–177. doi: 10.1111/imr.12386

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© 2016 Authors. Immunological Reviews Published by John Wiley & Sons Ltd

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Engineered hapten‐binding antibodies enable covalent payload attachment via hapten‐positioned spontaneous disulfide shuffling. (A) Structure of the Fab fragment of a digoxigenin‐binding antibody (PDB 3RA7). (B) Position of the engineered cysteine in the rim region of hapten‐binding antibodies which is in close proximity to the binding pocket of most hapten binders yet does not interfere with antigen binding. (C) Hapten‐positioned spontaneous disulfide shuffling links thiol‐containing haptenylated payloads to the antibody.