Chain Shuffling: Investigations into the Specificity and Selectivity of Antibody Catalysis

The antibody phage display system has been investigated as a vehicle for the potential altering of a catalytic antibody's specificity and chemical reactivity. Using previously identified catalytic antibodies, heavy and light “chain shuffling” experiments have been conducted. Catalytic activity and specificity requirements in terms of antibody complementarity‐determining regions were probed by interchanging heavy and light chain genes between antibodies that catalyze class‐similar but different chemical reactions with substrates that are enantiomerically opposed. The results were that antibody‐hapten binding specificity was only slightly altered, but catalytic activity was severely compromised.