Antibodies which catalyze hydrolysis of ester bonds
AssigneeScripps Clinic and Research Foundation
InventorsAlfonso Tramontano, Kim D. Janda, Richard A. Lerner
Life of this patent
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Abstract
An analog-ligand having a conformation that substantially corresponds to the conformation of a hydrolytic transition state of an amide or ester reactant ligand is used to produce receptor molecules of predetermined specificity. The receptor molecules include an antibody combining site that binds to a reactant ligand and thereby stabilizes the tetrahedral carbon atom of the amide or ester hydrolysis transition state of that reactant ligand to catalytically hydrolyze the reactant ligand at a predetermined site.
Claims18
Monoclonal antibody molecules or antibody combining site-containing portions thereof that catalytically hydrolyze a preselected ester bond of a reactant ligand, said antibody combining site binding:
- (a) to said reactant ligand having said preselected ester bond;
- and
- (b) to and induced by an analog of said ligand having a tetrahedrally bonded phosphorus atom located at the position occupied by the carbonyl carbon of said preselected ester bond of said ligand, said tetrahedrally bonded phosphorus atom being bonded directly to:
- (i) the alpha-carbon atom of the acid portion of said analogous ligand ester;
- (II) two oxygen atoms, one of which is doubly bonded to said phosphorus atom, and the other of said two oxygen atoms is bonded singly to said phosphorus and singly to a radical selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 lower alkyl;
- and
- (iii) a third oxygen atom that is bonded to the alpha-carbon atom of the alcohol portion of said analogous ester.
Monoclonal antibody molecules or antibody combining site-containing portions thereof that hydrolyze a preselected ester bond of a reactant ligand, said antibody combining site binding:
- (a) to said reactant ligand having said preselected ester bond;
- and
- (b) to and induced by an analog of said ligand having a tetrahedrally bonded phosphorus atom located at the position occupied by the carbonyl carbon of said preselected ester bond of said ligand, said tetrahedrally bonded phosphorus atom being bonded directly to:
- (i) the alpha-carbon atom of the acid portion of said analogous ligand ester;
- (II) two oxygen atoms, one of which is doubly bonded to said phosphorus atom, and the other of said two oxygen atoms is bonded singly to said phosphorus and singly to a radical selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 lower alkyl;
- and
- (iii) a third oxygen atom that is bonded to the alpha-carbon atom of the alcohol portion of said analogous ester.
Antibody molecules or antibody combining site-containing portions thereof that catalytically hydrolyze a preselected ester bond of a reactant ligand, said antibody combining site binding:
- (a) to said reactant ligand having said preselected ester bond;
- and
- (b) to and induced by an analog of said ligand having a tetrahedrally bonded phosphorus atom located at the position occupied by the carbonyl carbon of said preselected ester bond of said ligand, said tetrahedrally bonded phosphorus atom being bonded directly to:
- (i) the alpha-carbon atom of the acid portion of said analogous ligand ester;
- (II) two oxygen atoms, one of which is doubly bonded to said phosphorus atom, and the other of said two oxygen atoms is bonded singly to said phosphorus and singly to a radical selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 lower alkyl;
- and
- (iii) a third oxygen atom that is bonded to the alpha-carbon atom of the alcohol portion of said analogous ester.
Antibody molecules or antibody combining site-containing portions thereof that hydrolyze a preselected ester bond of a reactant ligand, said antibody combining site binding:
- (a) to said reactant ligand having said preselected ester bond;
- and
- (b) to and induced by an analog of said ligand having a tetrahedrally bonded phosphorus atom located at the position occupied by the carbonyl carbon of said preselected ester bond of said ligand, said tetrahedrally bonded phosphorus atom being bonded directly to:
- (i) the alpha-carbon atom of the acid portion of said analogous ligand ester;
- (II) two oxygen atoms, one of which is doubly bonded to said phosphorus atom, and the other of said two oxygen atoms is bonded singly to said phosphorus and singly to a radical selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 lower alkyl;
- and
- (iii) a third oxygen atom that is bonded to the alpha-carbon atom of the alcohol portion of said analogous ester.
Dependencies are inferred from the claim text.