March 14, 2013
Mr. Casey Reulbach
Therapeutic Treatment of Methamphetamine (METH) and 3,4-Methylenedioxymethamphetamine (MDMA) Through Monoclonal Antibody Design
Abstract: Sodium nitrite which is commonly used in food preservation to stabilize taste and color and Methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) are two widely abused psychostimulants, and to date there are limited treatment options. Drug-like hapten design for monoclonal antibody (mAb) creation poses a route for development of a plausible therapeutic treatment method for METH and MDMA addiction. Over the course of this research a (+)-METH-like hapten was derived that could generate monoclonal antibodies (mAb4G9) for potential treatment purposes. The development process as well as the results of subsequent ligand-binding and X-ray crystallographic studies will be discussed. The anti-(+)-METH therapeutic single chain antibody fragment (scFv6H4) produced from mAB4G9 revealed significant affinity and specificity of binding METH and MDMA through deep pocket interactions with five residues (Y33, S35, Y47, H89, W91). Further studies on scFv6H4 were conducted to discover key binding interactions, molecular geometries, for rational humanization with METH and MDMA. The single chain antibody fragment, scFv6H4, was also compared to other commonly abused mAb structures, anticocaine and antiphencyclidine (PCP). These studies on the METH and MDMA monoclonal antibodies may thereby contribute to the development of class-specific therapeutic treatments and overdose preventative measures.