Synthetic models in Chemical Biology

DNA is the key macromolecule used by nature to store the genetic information, therefore containing all the instructions that control the day-to-day function of cells. As such, it has been a traditional target for the development of different type of drugs, particularly anticancer agents. These drugs include alkylating agents, like cis-platinum and derivatives, and non-covalent binders like the anthracyclines, which interact to DNA by intercalation between base pairs. There are other types of cytotoxic non-covalent DNA binders, like distamycin or propamidine, which interact to DNA by insertion in the minor groove.

We have been interested in this latter type of molecules, because they are sequence selective and therefore provide for molecular engineering of site-specific DNA-promoted processes. In particular, we have designed and synthesized a number of variants of propamidine that work as sequence specific DNA optical sensors, or as light-activated prodrugs.

Some of the knowledge acquired in the studies of light-promoted processes has been extended to area of DNA-protein interactions. In particular, we have developed a chemical approach to control the DNA interaction of synthetic mimics of transcription factors, and expect that the tactic can be used in the future to regulate processes of gene expression.
Part of our work in this area is also focused to the construction of optical sensors that can detect minute amounts of transcription factors considered as oncogenic biomarkers, like the bZIP protein Jun.