Using the process of reactive immunization to induce catalytic antibodies with complex mechanisms: aldolases.
The process of reactive immunization has been used to induce efficient aldolase catalytic antibodies that use the enamine mechanism of natural enzymes. Reactive immunogens are those that react chemically during induction of the immune response. This same reaction is used later in catalysis. In essence one immunizes with the equivalent of a mechanism-based inhibitor. The difference is that instead of inhibiting a mechanism, a mechanism is induced. This advance allows the experimenter to dictate the exact mechanism by which catalytic antibodies proceed. The hapten used in the present study is a 1,3-diketone that both traps the requisite lysine residue to initiate formation of the enamine and induces a binding pocket that overcomes the entropic barrier of this bimolecular reaction.
Lerner
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Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Barbas
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D000096:Acetone / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D017151:Antibodies, Catalytic / Q000096:biosynthesis*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D007097:Imines / Q000737:chemistry / Q000378:metabolism; D007114:Immunization; D007659:Ketones / Q000494:pharmacology; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D013053:Spectrophotometry; D013379:Substrate Specificity
D000447:Aldehydes; D000906:Antibodies; D017151:Antibodies, Catalytic; D004791:Enzyme Inhibitors; D007097:Imines; D007659:Ketones; D000096:Acetone; D005634:Fructose-Bisphosphate Aldolase; D008239:Lysine