Semisynthetic Catalytic Antibodies
Our ability to carry out selective chemical transformations on biologically important molecules—including proteins, nucleic acids, and sugars—has been limited until recently to the specific reactions catalyzed by existing enzymes and the relatively indiscriminate reactions carried out by chemical reagents. The rational design of catalysts for the selective modification of structurally complex molecules would greatly impact on biochemistry, molecular biology, and medicine. Moreover, the synthesis and characterization of such catalysts should provide additional insight into the molecular basis for ligand-receptor recognition and catalysis. Crucial to the design of selective catalysts is the generation of highly selective binding sites. By taking advantage of the natural immune system, monoclonal antibody technology (Kohler and Milstein, 1975; Seiler et al., 1985) has made it possible to generate homogeneous ligand binding sites with enzymelike affinities and specificities. Antibodies have been selectively generated against biopolymers, such as nucleic acids, proteins, and polysaccharides, and smaller multifunctional molecules, such as steroids and prostaglandins. Antibodies bind ligands ranging in size from about 6 to 34 Å with association constants in the range of 104−1014 M−1 (Pressman and Grossberg, 1968; Goodman, 1975; Nisonoff et al., 1975). Antibody—ligand specificity is well illustrated by the following examples: antibodies generated against cis N-phenylmaleic acid monoamide bound the trans isomer with 103 lower affinity (Landsteiner and van der Scheer, 1934); antibodies against 3,17-androstenedione bound 3a, 17-dihydroxyandrostene with 103 lower affinity (Milewich et al.,1975).
KeywordsCatalytic Antibody Claisen Rearrangement Affinity Label Thiol Ester Catalytic Group
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