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

We have investigated DNA binding properties of a dicationic polyamide molec ule (GL020924) that has exhibited unique protein displacement and gene regu lation activities. Fluorescence, thermal melting and electrospray ionizatio n mass spectrometry experiments showed that the binding stoichiometry of GL 020924 is 2:1 to various DNA oligomers with 8-11 contiguous A/T bp. In acco rdance 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 GL0209 24-DNA complex may exhibit a novel form of stacking orientation involving a t least partially parallel peptide groups. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserv ed.