New strategies for the design of catalytic antibodies.
A new approach is advanced which is aimed at expanding the scope of antibody catalysis. It entails the design and synthesis of haptens that will elicit antibodies to catalyze acyl transfer reactions by a methodology which we term "bait and switch" catalysis. What we have done involves the placement of a point charge on the hapten in close proximity to, or in direct substitution for, a chemical functional group we wish to transform in the respective substrate. The haptenic charge should induce a complementary charge (on an amino acid residue) at the binding site. The substrate will lack this charge but will retain a similar overall structure. The monoclonal antibodies that bind these substrates now have the potential to act as general acids/bases for substrates having hydrolyzable functional groups.
Department of Molecular Biology and Chemistry, Research Institute of Scripps Clinic, La Jolla, California 92037.
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Janda
D000215:Acylation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002384:Catalysis; D004563:Electrochemistry; D006241:Haptens / Q000138:chemical synthesis / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure
D000911:Antibodies, Monoclonal; D006241:Haptens