Synthesis of a NAALADase Inhibitor: Towards the Development of a Quantitative PSMA Assay

Brent Griffith
University of Notre Dame

Prostate Specific Membrane Antigen (PSMA) is highly homologous to NAALADase (Fig. 1), the neuropeptidase that releases the neurotransmitter glutamate from N-acetylaspartylglutamase. For this reason, NAALADase has been selected as the target of an ongoing drug-design project based at the University of Notre Dame. This study focuses on the use of these NAALADase inhibitors as potential diagnostic markers for prostate-derived cells and in the treatment of prostate cancer.

The synthesis of one such inhibitor (Scheme 1) and its use as a reference in the development of a high-throughput, Surface Plasmon Resonance based, PSMA assay are the primary objectives of this study. This assay will be used to test the efficiency of the inhibitor in the detection of PSMA as well as for the automated analysis of a library of other potential inhibitors.