The combination of systemic toxicity, water insolubility and a labile chemical structure has limited the clinical use of diethylstilbestrol (DES) 1 for the treatment of prostate cancer. To determine if DES could potentially be a prodrug substrate for the pre-targeting strategy known as antibody directed enzyme prodrug therapy (ADEPT), the DES-glutamate 5 was prepared. The synthesis required the activation of the bis-t-butyl glutamate ester 2 to the isocyanate 3 followed by addition of DES 1. The desired DES-glutamate 5 was water-soluble and upon incubation with carboxypeptidase G2 (CPG2) underwent carbamate cleavage to give DES 1. A control reaction in the absence of CPG2 demonstrated that the enzyme was necessary for rapid glutamate cleavage to give DES 1. HPLC analysis was required to follow the reaction of DES-glutamate 5 with CPG2. These preliminary results suggest that it may be possible to examine an ADEPT strategy for DES provided enzymatic kinetics can be measured.