Insight into DNA Minor Groove Unspecific Binding of Pyrrole Polyamide

Chemistry-based approaches have exploited base-pairing for sequence-specific recognition of DNA. A variety of sequence-specific Py-Im hairpin polyamides to target sequences of biological interest have been widely developed. Here we reported that an eight-ring N-methylpyrrole polyamide can induce a strong negative signal when it interacted with ct-DNA in the minor groove, which differs from the typical CD signal induced by hairpin polyamide reported previously. Our current efforts mainly focused on investigating possible reasons and binding mode by CD spectroscopy, singular value decomposition, and atomic force microscopy. The results suggested that partly compacted DNA may form due to the unfolded binding mode that made DNA shrink along the axis of duplex. In addition, this unfolded binding was remarkably restrained in high ionic strength medium where the neutralized phosphate groups in the DNA backbone narrowed the minor groove. The present work might help to understand deeply how the Py-Im polyamides bind to duplex DNA under different conditions and, in particular, be applied to gene manipulation and expression.