A novel dicationic polyamide ligand binds in the DNA minor groove as a dimer.

We have investigated DNA binding properties of a dicationic polyamide molecule (GL020924) that has exhibited unique protein displacement and gene regulation activities. Fluorescence, thermal melting and electrospray ionization mass spectrometry experiments showed that the binding stoichiometry of GL020924 is 2:1 to various DNA oligomers with 8-11 contiguous A/T bp. In accordance with those findings, circular dichroism experiments showed GL020924 binds as a partially staggered side-by-side dimer spanning 10-12 bp. These observations and molecular modeling studies demonstrate that the 2:1 GL020924-DNA complex may exhibit a novel form of stacking orientation involving at least partially parallel peptide groups.