Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
Targeting double-stranded DNA with small molecules remains an active area of basic research. Herein is described a cyclic DNA bisintercalator that is based on two naphthalene diimide (NDI) intercalating units tethered by one linking element specific for binding in the minor groove and the other linking element specific for binding in the major groove. DNase I footprinting revealed a strong preference for binding the sequence 5'-GGTACC-3'. NMR structural studies of the complex with d(CGGTACCG)(2) verified a pseudocatenane structure in which the NDI units reside four base pairs apart, with one linker segment located in the minor groove and the other in the major groove consistent with the linker designs. To the best of our knowledge, this is the first structurally well-characterized pseudocatenane complex between a sequence specific cyclic bisintercalator and intact DNA.