Interaction of aminoacridines with deoxyribonucleic acid: Effects of ionic strength, denaturation, and structure

Abstract

SynopsisThe 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. 136DHUMMOND, SlMPSON-G1LDISMEISTISR, AND PEACOCKE a spectrophotonietxic method and by equilibriuiii dialysis, it was inferred5 that there are two stages in the interaction: process I, a strong binding of individual proflavirie cations up to r -0.2;* followed by process 11, an extensive, but weaker, binding of proflavine cations up to the maxi niuni of 7' = 1.0. For various reasons it was concluded5 that, in process I, the binding forces were both the electrostatic interaction of acridine cations with DNA phosphate groups and the attractive forces between acridine rings and base rings of the D S A ; and that, in process 11, the binding was caused by mutual interaction between different proflavine cations. This interpretation s e e m to have fourid general acceptance (e.g., review of Steiner and Beers6). Bradley et al.7-q investigated spectrophotonietrically the aggregation of dyes, i n particular acridirie orange, when they are bound 1 o polynucleotide anions. They distinguished between : complex I, in which 1' + 1.0 and there is extrrisive interaction between ligand niolecules with characteristic. spectral shifts (this is equivalent to process 11, above) ; and complex 11, in which 1' << 1.0 and ligarid molecules are sufficiently separated 011 the macromolecule not to interact with each other (equivalent to process I, above; the terminology of Peacocke arid Skerrettj will be used henceforth, except that T will usually be the same as their 7'1, referring to binding by process I).E'roni various observations oil the viscosity, sedimentation coefhicnt, and x-ray diffraction patterns of coniplexes of DKA arid proflavine, Leriiian'O concluded that in...

The effect of dose and time on the induction of genetic alterations insaccharomyces cerevisiae by aminoacridines in the presence and absence of visible light irradiation in comparison with the dose-effect-curves of mutagens with other type of action

“…In accordance with DNA-aminoacridine intercalation models which explain binding form one (Lerman, 1963;Drummond et al, 1965), the aminoacridine molecule still intercalates between successive nucleotide bases. AO, whose structure might render intercalation more difficult, is in this regard at a disadvantage when compared to PF.…”

Chance and Necessity in Arthur Peacocke's Scientific Work

“…He continued to study the structure of "naked" DNA but also started to work on DNA isolated from cells still wrapped in proteins that normally accompany it inside cells. Among the studies on "naked" DNA was the work that resulted in a long series of highly noted publications on the binding of various dyes to RNA and DNA, and the effects of such molecules on the structure, and in later works the function, of nucleic acids (Drummond, Simpson, et al 1965;Blake and Peacocke 1966;Drummond, Pritchard, et al 1966;Nicholson and Peacocke 1966;Pritchard, Blake, et al 1966;Blake and Peacocke 1967a, b;Blake and Peacocke 1968;Lloyd, Prutton, et al 1968;. Most of the dyes that Peacocke studied fit into the category known as DNA intercalating agents; such molecules bind specifically to DNA by fitting into the inner structure of the DNA double helix and find their way to fit into a space between DNA bases.…”

Use of the 295- to 300-Nanometer Circular Dichroism Trough of Ribonucleic Acid to Study Helix Winding: Effect of Acridine Orange

“…These observations suggested that the dye might modify the conformation of the polymer, but this was not observed directly (12). In (6).…”