Modified Intercalation Model for the Interaction of Amino Acridines and DNA

Abstract

THE binding of amino acridines to DNA (Fig. 1) has been shown to occur by both a strong and a weak binding process¹. The energy and specificity of the strong binding process are too great for the interaction to be purely electrostatic and it has become clear that interaction of the acridine ring with the bases in DNA is involved^2–5. Lerman⁶ postulated that the binding process involved an intercalation of the amino acridines between base pairs in the ordered array of DNA with a consequent extension and local untwisting of the DNA double helix. Estimates have been made by various authors of the extent of untwisting which is possible for the DNA structure and which is required to allow intercalation; these vary from 12° (ref. 7) to 45° (ref. 6, an angle of −9°, in the left-handed sense, between successive base pairs). The plane of the intercalated amino acridines was thought to be perpendicular to the helix axis and this has been verified within the broad limits of the experimental methods^8,9. Evidence for extension of the DNA helix on binding amino acridines has been obtained by autoradiography¹⁰ and X-ray^11,12, sedimentation⁶ and viscosity^6,13 studies. In his 1961 paper, Lerman proposed that the amino acridine was located over a base pair of the DNA (Fig. 2). Denaturation of the DNA disrupts the ordered arrays of base pairs in the double helix, apart from limited local renaturation, and, on the basis of the above intercalation model, would be expected to remove or, at least, greatly to reduce such strong binding. Many observations show that this is not the case and that the strong binding process is not reduced in extent by denaturation; this has been shown for amino acridines^14,15 and for similar organic cations¹⁶. On the basis of model building studies we wish to propose a modified intercalation model which satisfies these criteria and, in particular, the condition that binding should occur to the same extent on denatured DNA.