Antibodies which catalyze hydrolysis of ester bonds

DETAILED DESCRIPTION The present invention contemplates a receptor molecule that contains an antibody combining site or idiotype-containing polyamide that is capable of catalytically hydrolyzing a preselected carboxylic acid and amide or ester bond of a reactant ligand.
That antibody combinining site binds to (immunoreacts with): (a) a reactant ligand containing that preselected carboxylic acid amide or ester bond, and (b) a ligand analogous to the reactant ligand that contains a tetrahedrally bonded atom such as a phosphorus atom at a position analogous to that of the carbonyl carbon atom of the preselected carboxylic acid amide or ester bond of the reactant ligand.
The hydrolytic transition state of the reactant ligand so bound contains a tetrahedral carbon atom bonded to (a) a carbon atom, the alpha-carbon of the acid portion of the ester or amide, (b) two oxygen atoms, and (c) the oxygen atom of an ester or the nitrogen atom of an amide.
Molecules containing an idiotype raised to the hydrolytic transition state of a reactant ligand are raised or induced by immunizing with analog-ligand molecules (preferably bound to a protein carrier to form a conjugate) containing an analog of a hydrolytic transition state of the ligand.
The immunizing analog-ligand hydrolytic transition state molecule contains a tetrahedrally bonded central atom, such as phosphorus, bonded directly to (a) a carbon atom of the acid portion of the analogous ligand amide or ester, (the alpha-carbon of the acid portion) (b) two oxygen atoms and (c) a third oxygen atom or a nitrogen atom, the third oxygen atom or nitrogen atom being bonded to the alpha-carbon atom of an analogous ester or amide of the ligand.
The alpha-carbon atom of the acid portion, (a) above, bonded directly to the central tetrahedral such as phosphorus atom of the analog-ligand molecule, is included in a chain that contains at least 5 atoms, and more preferably at least about 15 atoms and including a substituted phenyl group, as is the third oxygen or nitrogen atom, (c) above