The project includes organic synthesis and biological evaluation of carbocyclic nucleoside analogs that are envisioned to selectively modulate the activity of specific components of DNA-processing molecular machinery (namely DNA polymerase alpha and ribonucleotide reductase). Combined with e.g. the selective CHK1 inhibitor we developed recently, they might induce the synthetic lethal phenotype in cancer cells. Also proposed is the synthesis of aza- and carbocyclic analogs of the DNA polymerase alpha inhibitor – dehydroaltenusine. The overarching concept of the proposed research is finding novel agents that would be useful in the treatment of cancer. The proposed research efforts will be part of a compact medicinal chemistry program that will include several research groups.