ISSN:
0006-3525
Keywords:
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A theory of polyelectrolyte effects on site-binding equilibria is generalized to multivalent ligands, multivalent supporting salt, intercalation, and multiple-site exclusion. The theory, which contains no adjustable parameters, except the number of sites excluded by a bound ligand, gives the dependence of the equilibrium constant on the binding fraction and the salt concentration. The theory is compared with prior experimental data for the dissociation of poly(acrylic acid), the binding of magnesium to polyphosphate, and the binding of ethidium and actionomycin D to DNA. The theory predicts the binding fraction dependence of the dissociation constant of poly(acrylic acid) well. The theory predicts the binding fraction dependence of the association constant of the binding of Mg2+ to polyphosphate well, if either one or two phosphates are bound by a magnesium ion. We conclude that polyelectrolyte effects on drug-DNA equilibria must be substantial. It follows that an incorrect estimate of the number of sites excluded by a bound drug molecule (because of its size or some other nonpolyelectrolyte effect) can be obtained from binding data if polyelectrolyte effects are ignored. The estimate is also within the context of, and subject to the validity of, the model used to describe the nonpolyelectrolyte contribution to binding. Our results suggest that, subject to these conditions, the anticooperativity of the binding of ethidium to DNA might be explained solely in terms of polyelectrolyte effects, and without reference to multiple-site exclusion, if sequence-specificity effects can be safely ignored. Our results also suggest that as few as two base pairs might be excluded by an actinomycin molecule. The theory gives fairly good agreement for the salt-concentration dependence of the association constant of all of the systems studied, including the complex of the neutral drug actinomycin with DNA.
Additional Material:
17 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bip.360231202
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