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...
SynopsisThe intrinsic viscosities at zero shear rate of defined complexes of proflavine, 9-aminoacridine, and g-amino-l,2,3,4tetrahydroacridine with calf thymus DNA have been determined at various ionic strengths by means of rotating cylinder viscometers. By controlled adjustment of the composition of the mixtures, the amount of bound acridine ( T moles/g.-atom DNA phosphorus) was maintained constant at different. dilutions. The intrinsic viscosities of the complexes increased with T up to r values (ca. 0.16-0.20) corresponding to the end of the process of strong binding of the acridinium cations. However, complex formation between the acridines and thermally denatured DNA caused either a marked decrease in viscosity (at the low ionic strengths of 0.0015 and 0.005) or no change a t all (ionic strength 0.1). These results are discussed in the light of presently available hydrodynamic theories relating the intrinsic viscosity of DNA to its molecular extension.When aminoacridines are bound to DNA in solution changes occur in the properties of the DNA solutions which suggest that the DNA has become more extended.'V2 This is consistent with an earlier observation3 of formation of a stable gel when enough positive cations of proflavine, 3,6-diaminoacridine1 were bound to DNA to neutralize all the negative charges on the DNA (r = 1). It has frequently been pointed out that the proflavine cations probably rest on the flat rings of the nucleic acid bases; for example, the ljgand molecules have to have a minimum flat area in order to be strongly bound.3 This strong binding (process I of Peacocke and Skerrett3) has a maximum limit of about 4 or 5 proflavine cations for every turn of the double helix (r 2 0.2-0.25). At higher concentrations of free proflavine, a weaker binding process (11) becomes dominant and appears to be chiefly dependent on proflavineproflavine interactions. Lermanl observed a marked increase in the viscosity of DNA solutions when acridines were bound, e.g., at r = 0.13-0.21, the viscosity increased by a factor of the order of three. Although a provisional interpretation of these increases in viscosity was attempted' it could not be securely based, since the observed viscosity values could not be reliably extrapolated to zero shear rate from the values observed at the lowest shear rate (ca. 30 see.-') obtained with capillary viscometers; 971
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