A NEW CLASS OF POLYINTERCALATING MOLECULES

We have synthesized a series of polyintercalating compounds, including the first known tetraintercalator, based on the 1,4,5,8-naphthalenete tracarboxylic diimide chromophore. The chromophores are attached in a head-to-tail arrangement by peptide linkers and are synthesized by sta ndard solid phase peptide synthesis methods. We report evidence, based on UV-visible spectroscopy and viscometry, that the compounds are ful ly intercalated upon binding to double-stranded DNA. Using DNAse I foo tprinting experiments, the bisintercalator 2 was found to bind to DNA in a cooperative manner. The footprinting results as well as associati on and dissociation kinetics data reveal that the compounds exhibit a tremendous preference for GC over AT sequences. A. mode of binding is proposed in which the compounds intercalate completely from the major groove, and not in a threading manner as may be suggested by their str uctures. A kinetic scheme is proposed that takes into account the obse rved cooperativity and fits the data for the dissociations of the poly intercalators from poly(dAdT), although a similar scheme could not ade quately model their dissociations from poly(dGdC) or from calf thymus DNA.