The objectives of the proposed research are: 1. To determine the structure-activity relationships and mode of action of the 2,2-dimethyl phosphoraziridines as radiation potentiating antitumor agents and to optimize the design of new agents. This involves the synthesis of new compounds designed to have either phosphorylating or alkylating activities, or both; comparative studies of their chemical and biochemical activities, and radiation potentiating effects in cell-culture systems and in animal tumors; and studies of the interaction of selected agents with DNA-repair at the molecular level and of their reactions with nucleic acid components. 2. To synthesize and study new derivatives of partially thiolated polynucleotides designed to improve their selectivity and/or stability as antitemplates (inhibitors) of DNA polymerases in vitro and in vivo, and to synthesize and study modified oligonucleotides of known base sequences as specific """"""""antiprimers"""""""" of reverse transcriptases. Studies include physicochemical characterization, stability to nucleases, inhibition of polymerases, and cytotoxicity.
