A simplified illustration to show DNA breathing, a concerted dynamical process in limited DNA regions that combines base pair unstacking with the transient rupture of hydrogen bonds connecting base pairs. Base pairs undergoing H-bond breakage in higher energy beta-DNA regions are shown in the dashed oval area. Lower energy beta-structural elements on either side are marked with asterisks. See text for discussion.

Intercalators that necessitate the transient rupture of hydrogen bonds connecting base pairs to gain entrance into (and exit out of) DNA (i.e., meso-tetra [4-N-methyl (pyridyl) porphine]) constitute convincing evidence that DNA breathing and drug intercalation are related phenomena.

Echinomycin is an example of a bifunctional intercalator that has two quinoxaline ring systems, separated by 10.2 Angstroms, connected through amide linkages to a rigid octapeptide chain. The stereochemistry of this naturally occurring DNA binding antibiotic allows both quinoxaline ring systems to intercalate simultaneously into neighboring high-energy beta-structural elements. The molecule is a valuable probe to understand the detailed stereochemistry of DNA breathing.