Science · 1997 · 209 citations · 31 references
PharmacyBiochemistryBiotechnologyBiocatalysisCatalysisCombinatorial ChemistryAntibody DiscoveryAntibody Library ConstructionAntibody ScreeningAntibody-antigen RecognitionCatalytic MechanismsEnzyme-substrate RecognitionAntibodiesAntibody Library DesignCatalytic SpecificityCombinatorial Antibody EngineeringDirect SelectionFilamentous Phage VectorsHuman Hybridoma TechnologySelection
The immune system has been used as a source of de novo catalysts, but its full potential requires a system that directly selects for specific functions. The authors devised a filamentous phage‑based method that chemically selects catalytic antibodies, preserving hybridoma advantages while avoiding limitations of biologically based selection. Catalytic antibodies exhibit chemoselectivity, enantioselectivity, significant rate acceleration, and can reroute reactions, enabling catalysis for processes lacking natural or synthetic enzymes.
For the past decade the immune system has been exploited as a rich source of de novo catalysts. Catalytic antibodies have been shown to have chemoselectivity, enantioselectivity, large rate accelerations, and even an ability to reroute chemical reactions. In many instances catalysts have been made for reactions for which there are no known natural or man-made enzymes. Yet, the full power of this combinatorial system can only be exploited if there was a system that allows for the direct selection of a particular function. A method that allows for the direct chemical selection for catalysis from antibody libraries was so devised, whereby the positive aspects of hybridoma technology were preserved and re-formatted in the filamentous phage system to allow direct selection of catalysis. This methodology is based on a purely chemical selection process, making it more general than biologically based selection systems because it is not limited to reaction products that perturb cellular machinery.
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Continuous cultures of fused cells secreting antibody of predefined specificity
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William D. Huse, Lakshmi Sastry, Sheila A. Iverson et al. · Science · 1989 · 805 citations