Interaction of Aminoacridines with Deoxyribonucleic Acid: Effects of Ionic Strength, Denaturation, and Structure I>. S. DRUnInlOND, V. F. W. SIRlPSO?\r-CrILDE~IEISTER, arid A. It. PEACOCKE, Departnients of Biochemistry and Clinical Biocheinistiy, 7niver.sily qf Oxford, England
Synopsis
The binding crirves of various arniiioacridines on calf thymiis DNA have been determined by a spectrophotometric method. The dominant role of electrostatic forces in the interaction has been confirmed by the effect of ionic strength. Side chain and ring sri1)stitiients in the amirioacridines do riot inhibit binding. since this decreases in the order: arrariil > neoniotiacriti > atebrin > !I-aminoacridineproflavine > Y-amino-1,2,3,4-tetrahydroacriditie (THA). The last named shows the effect, of diminishing the flat area of the rings in the amiiioacridines. The shape of t,he binding ciirves of proflavine, S-aniiiroacridirie, and THA on thermally denatiired DNA show that, sborit 30-.50':( more binding sites are available to these cations on denatured DNA than oii native I>NA, bat that the binding constants a,re the same. These observations are discrissed in relatioii to the intercalation and other models for t,he interaction. It is coriclrtded that exact and complete intercalation is not a necessary condition of strong binding and that other, less regular, models, iii which the positjive ring nitrogens of the acridines are close to the DNA phosphates and the acridine rings partially interact with the 1)NA base rings, are prohably more consistent with i,he effect of denatiiration of I)NA on the h i d i n g ciirves which are characteristic of the interaction in sohition.
* Here and elsewhere: T = number of ligarid moleciiles borirrd per atom of I)NA phosphorus; c = concentration of free, nnbor~nd, hgand in solution in moles/liter.; 12 = maximiim valire of r ; M(P) = molarity of DNA phosphorus.