Development of Antibodies for Drug Metabolizing Enzymes

We will develop and market a comprehensive collection of antibodies specific for enzymes that play a significant role in drug metabolism . Availability of specific antibodies will greatly facilitate studies of polymorphisms, species and tissue distribution of drug metabolizing enzymes, and the role of individual enzymes in the metabolism of endogenous and xenobiotic chemicals. Widespread availability of specific antibodies will overcome current limitations. Some of these limitations include restricted access to antibodies, differences in specificity between preparations, and lack of specificity for many antibodies. We have already developed several goat antibodies directed against rabbit cytochromes P450; antibodies specific for prostaglandin H synthase, including anti-peptide antibodies specific for the recently discovered mitogen inducible PGHS-2, may exhibit a different spectrum of xenobiotic activation than PGHS-1. We are currently developing anti-peptide antibodies specific for mammalian lipoxygenases, which are also implicated in xenobiotic metabolism. However, we are well aware of the primary need for additional antibodies specific for P450 isoforms. We will therefore: (a) acquire available form-specific monoclonal and polyclonal antibodies by licensing form academic laboratories where possible, (b) to develop a series of anti-peptide antibodies and recombinant protein standards to the major P450 isoforms, and (c) to extensively characterize the specificity and reactivity of these antibodies in standard assays.