research

DNA Intercalators as antitumor therapeutics

Our group is interested in investigating the interactions of small molecules with DNA, and using these interactions to design new therapeutics. In particular, this project is focused on targeting a newly discovered DNA motif, the guanine quartet. In contrast to the regular Watson-Crick A-T or G-C base-pairing, this association mode of DNA brings together four guanines into one structure (Scheme 1). Indirect evidence points to the fact that the chromosome ends in our body, which have guanine rich regions, fold up into this interesting motif (Scheme 2).

What is particularly attractive about the G-quartet is that it can serve as the target for a new generation of antitumor therapeutics. Our group is thus actively involved in searching for small molecules which bind the G-quartet, and exhibit antitumor activity. Specifically, we have synthesized aromatic molecules, which are designed to bind and stabilize the G-quartet by insertion of their aromatic moiety between the associated guanines of the folded telomere (Scheme 3). This phenomenon is called "intercalation".
This project involves the synthesis of these molecules and examination of their binding to the guanine quartet motif in order to optimize their antitumor activity. Many techniques can be learned on the way: small molecule synthesis, DNA synthesis, evaluation of the binding of drugs to DNA, as well as molecular modeling.