Antibody combining sites that exhibit amide or ester synthase activity
AssigneeScripps Clinic and Research Foundation
InventorsStephen Benkovic, Richard A. Lerner, Alfonso Tramontano, Andrew D. Napper
Life of this patent
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Abstract
A phosphorous-containing analog-ligand having a conformation that substantially corresponds to the conformation of an amide- or ester-forming transition state is used to induce production of receptor molecules whose antibody combining sites have amide or ester synthase catalytic activity when reacted with a ligand containing (i) a carbonyl carbon atom and (ii) an amine or alcohol group that are structurally capable of forming a preselected carboxylic amide or ester bond.
Claims6
An amide or ester synthase comprising a monoclonal receptor molecule containing an antibody combining site capable of catalyzing the formation of a preselected carboxylic amide or ester bond, said combining site binding:
- (a) to a ligand containing (i) a carbonyl carbon atom and (ii) an amine or alcohol group that are structurally capable of forming said preselected carboxylic amide or ester bond;
- and
- (b) to an analog-ligand wherein the analog-ligand is structurally analogous to said preselected amide or ester, said analog-ligand having a tetrahedrally bonded phosphorus atom located at the position occupied by said carbonyl carbon atom of said preselected carboxylic amide or 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 ligand by a single bond;
- (ii) a first oxygen atom that is doubly bonded to said phosphorous;
- (iii) a second oxygen atom that is bonded to said phosphorous atom by a single bond, and is singly bonded to a radical selected from the group consisting of C.sub.1 -C.sub.6 lower alkyl, benzyl and phenyl;
- and
- (iv) a third oxygen atom or a nitrogen atom singly bonded to said phosphorous atom, and is also singly bonded to the alpha-carbon atom of the amine or alcohol portion of said ligand.
A monoclonal receptor molecule secreted by a hybridoma designated 24B11 and HB9488, whose antibody combining site immunoreacts with a ligand having a structure of the formula ##STR9##
Dependencies are inferred from the claim text.