Pendant NDI bisintercalator derivatives

Sequence specific binding of DNA by small molecules potentially offers the ability to control gene expression. In the past, our laboratory has developed sequence specific threading polyintercalators based on naphthalene diimide (NDI) groups linked head-to-tail by peptides. This design yielded a tetraintercalator with the ability to bind its specific 14 base pair site with a 57 day dissociation half-life, a record for a synthetic DNA-binding molecule (Rhoden Smith and Iverson, 2013). A longer hexaintercalator binds specifically to a 22 base pair site, the longest for a synthetic non-nucleic acid based-DNA binding molecule (Rhoden Smith and Iverson, 2013). The following work attempts to expand our family of DNA binding molecules by focusing on an alternative bisintercalator design where peptide backbones vary while incorporating NDI units at the ε-amino group of lysine residues, as initially proposed by Dr. Chelsea Martinez (Martinez, 2011). Several pendant or comb-like polyintercalator derivatives analyzed by DNase I footprinting show a preference for GC-rich sequences.