David Weiner

Phosphorodithioates: synthesis and evaluation of new haptens for the generation of antibody acyl transferases

Abstract An extension of the transition state analogue (TSA) hapten approach for the elicitation of catalytic antibodies for acyl-transfer reactions is described. It is based on the enlistment of phosphorodithioate 1 as a stable mimic of the putative tetrahedral intermediate (TI − ) formed during the base-catalyzed hydrolysis of bisaryl carbonate 2 . Six members of a library of 25 monoclonal antibodies elicited to 1 catalyze the hydrolysis of 2 . The most efficient catalyst, 48F10, exhibits Michaelis-Menten kinetics [ K m (2)=686 μ M, k cat (2)=2.7 min −1 , k cat (2) k uncat (2) =3×10 4 ] and is one of the most active carbonate hydrolyzing antibodies yet reported. This report highlights the utility of haptens that incorporate substitution of the non-bridging phosphorus(V) oxygen atoms present in the more classical TSA approaches with sulfur, to elicit efficient catalysts for acyl-transfer processes.

Design, synthesis and characterization of panning agents for the selection of metalloantibodies

The design, synthesis and characterization of a new class of metal complexes (panning agents) for the selection of antibodies from a combinatorial library are described. The metal panning agents contain a phosphorodithioate moiety that binds soft metals, leaving them coordinatively unsaturated. Subsequent panning against an antibody phage library selects for members that recognize, and bind directly to, the metal rather than ligands attached to the metal.