Investigations using immunization to attenuate the psychoactive effects of nicotine.

Despite the enormous health risks, people continue to smoke and use tobacco primarily as a result of nicotine addiction. As part of our immunopharmacotherapy research, the effects of active and passive immunizations on acute nicotine-induced locomotor activity in rats were investigated. To this end, rats were immunized with either a NIC-KLH immunoconjugate vaccine designed to elicit an antinicotine immune response, or were administered an antinicotine monoclonal antibody, NIC9D9, prior to a series of nicotine challenges and testing sessions.

Experimental determination of the absolute enantioselectivity of an antibody-catalyzed Diels-Alder reaction and theoretical explorations of the origins of stereoselectivity.

The exo and endo Diels-Alder adducts of p-methoxycarbonylbenzyl trans-1,3-butadiene-1-carbamate and N,N-dimethylacrylamide have been synthesized, and the absolute configurations of resolved enantiomers have been determined. On the basis of this information, the absolute enantioselectivities of the Diels-Alder reaction catalyzed by antibodies 13G5 and 4D5 as well as other catalytic antibodies elicited in the same immunizations have been established. The effects of different arrangements of catalytic residues on the structure and energetics of the possible Diels-Alder transition states were modeled quantum mechanically at the B3LYP/6-311++G**//B3LYP/6-31+G** level of theory.

Antibody-catalyzed cleavage of the D-Ala-D-Lac depsipeptide: an immunological approach to the problem of vancomycin resistance.

Vancomycin resistance is currently a major healthcare problem. The development of a catalytic monoclonal antibody (mAb) that hydrolyzes the D-Ala-D-Lac depsipeptide provides a potentially novel antibiotic strategy. A phosphonate hapten design was used to program antibody catalysis.

Monitoring Chemical Warfare Agents: A New Method for the Detection of Methylphosphonic Acid.

Methylphosphonic acid (MPA) is the degradation product of many chemical warfare agents. The convenient detection of this substance would aid in field testing to confirm illicit manufacture and use of banned chemical weapons. Efficient functionalization of MPA with an aromatic diazo compound allowed binding by monoclonal antibodies elicited by using an analogous hapten (see scheme).