A New Look at DNA Intercalation is DNA Intercalation Something Artificial or Highly Biologically Relevant?

Abstract

Potential roles of intercalative binding have challenged researchers since Lehrman's discovery 50 years ago, that aromatic molecules may reside in between base-pairs. Lately intercalation was found to be used also by bigger systems like operatory proteins. DNA-Recombinases and TATA-box binding protein use intercalative binding for indirect readout of DNA sequences. In such complexes DNA adopts diverse conformations. Using polarized-light spectroscopy and molecular modeling we study DNA complexes with synthetic ruthenium compounds [(L)3Ru]2+ or [dppz(L)2Ru]2+ (L=phenanthroline or bipyridine). We find that depending on level of hydrophobicity, chirality, and size of intercalating moiety DNA indeed adopts different final geometries. With Δ-[dppz(phenanthroline)2Ru]2+ with dppz as intercalating moiety DNA locally converts to an A-like form with characteristic bases roll and sugar-puckering. Not least interesting is DNA bending of 35o induced by partial, “wedge”, intercalation of phen-ring system of Δ of [phen3Ru]2+ compound. In conclusion, by imitating operatory proteins intercalative binding by small DNA-binding ligands could be used in a variety of ways: for modulating local base and sugar conformation, as well as introducing major changes such as bending in the DNA helix structure.Fig 1. DNA bends significantly upon “wedging” intercalation of [phen3Ru]2+(b), analogously to the observed bending caused by the TATA-box binding protein (a).