The synthesis of prodrugs derived from PaTrin-2

Abstract

Chemotherapeutic alkylating agents, like triazenes and nitrosoureas, whose mechanism of action involves the modification of guanine residues at the 06 -position in DNA are often rendered ineffective by the repair enzyme ATase. Found in all cells, A Tase (O6 -alkylguanine-DNA alkyltransferase) is responsible for the removal of the introduced alkyl groups from the 06 -atom of guanine. Inactivation of ATase by the administration of pseudosubstrates prior to chemotherapy has been shown to enhance the cytotoxic effects of subsequently administered alkylating agents.