Synthesis of peptide-diazeniumdiolate conjugates: towards enzyme activated antitumor agents

The development of NO donors with site-specific and time-controlled properties is of great interest. We have designed a novel prodrug class as possible agents against metastatic prostate cancer by coupling a diazeniumdiolate to the terminal carboxyl groups of amino acids or peptides, such as Ser-Ser-Tyr-Tyr, Ser-Ser-Phe-Tyr, and Gly-Ile-Ser-Ser-Phe-Tyr. These prodrugs can be activated by α-chymotrypsin or prostate specific antigen and are potentially potent compounds for prostatic cancer.