Compounds which alkylate DNA have proven useful in the treatment of a variety of cancers; however these compounds suffer from numerous adverse effects including myelosuppression, nausea, vomiting, hair loss and secondary cancers arising as a result of the lack of selectivity of the currently available antineoplastic agents. Improving the selectivity of such agents and targeting specific genes has emerged as an important strategy to improve the effectiveness of alkylating agents. Our lab has been involved in the design and synthesis of minor groove alkylators of DNA with the goal of targeting specific DNA sequences and suppressing the expression of genes involved in cancer (oncogenes). To accomplish this goal we utilize a number of different molecular modeling programs to create virtual molecules and predict their binding to specific sequences of DNA. Once the synthetic targets have been identified, the compounds are synthesized in our lab. Much of the work involves the application of organic synthesis to produce the target molecules which are subsequently tested by the National Cancer Institute. Selected Publications: Synthesis of 1,2,3,12a,12b Hexahydro cyclopropa[1,2¬-d]benzo[f]pyrrolo[1,2 b] isoquinolin 5,7 dione Related to Duocarmycins and Anthramycin. Atigadda Venkatram, Tara Colley, Jack DeRuiter, Forrest Smith* Journal of Heterocyclic Chemistry, 2005, 42, 297-301.