Polyelectrolyte effects on site-binding equilibria with application to the intercalation of drugs into DNA.
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Biomedical subjects
Publications and source records attributed to G S Manning.
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A patient had a parathyroid adenoma and prolactin-secreting pituitary tumor, suggestive of the multiple endocrine neoplasia (MEN) I syndrome. The presence of a marfanoid habitus--found more typically in MEN III syndrome--as well as mitral valve prolapse, mental retardation, and bilateral optic atrophy suggests a new variant of the MEN syndrome, possibly representing widespread dysplasia of endocrine and other tissues.
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The effect of counterion-counterion repulsion on the orientation of DNA, a polyion of high charge density is examined by electric-field orientation experiments. The charge species of the counterion and the ionic strength effect the orientation in a manner consistent with a theoretical treatment of the polarization of high charge density polyelectrolytes in terms of the effect of the applied field on the equilibrium distribution of condensed counterfoils on the polyion.
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Counterion binding to polyelectrolyte chains is formulated as a chemical reaction Mz (free) leads to Mz (bound). Expressions for the chemical potentials of free and bound counterions are set equal to obtain the reaction equilibrium. The results are equivalent to those in the previous paper of this series. An additional result obtained here is that a polyion holds its bound counterion layer with a strength on the order of 100 kcal/(mole cooperative unit). The method is then applied to the calculation of the polarizability along the chain due to the bound (condensed) counterions.
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The limiting laws for polyelectrolyte solutions developed in previous papers of this series have been amply confirmed by measurement. A surprising result of the accumulated data is that the limiting polyelectrolyte charge fraction (fraction of fixed charges uncompensated by condensed counterions in the limit of zero concentration), persists up to concentrations of 0.1 M or even higher. Here the theory is extended in a simple manner to finite concentrations, and the stability of the charge fraction is found to be firmly based on consequences of the long-range polyelectrolyte field. The associated counterions are assumed to translate freely in a region centered on the contour axis of the polyion. The numerical value of the free volume is determined self-consistently from the axial charge density of the polyelectrolyte and is used as the general framework within which specific binding effects are treated.
A simple theoretical equation for the binding of Mg2+ to DNA in the presence of excess 1:1 salt is derived from a model that does not specify discrete binding sites but rather allows the associated metal ions to move freely near the surface of the DNA polyion. Use of a numerical value for the free volume, determined uniquely, in a separate communication, by a free energy minimization, leads to predicted values for the Mg2+ binding constant that are in essential agreement with measured values taken from the literature.
An extension to polyelectrolyte solutions of Onsager's field-dissociation relation for weak electrolytes can be derived in a simple way. It is found that, except in the limit of zero ionic strength, a strong applied electric field prevents counterion condensation from proceeding to completion. The extent of incompleteness initially varies linearly with the applied field. The field-dissociation relation can easily be incorporated into the theory of ionic effects on the stability of ordered polynucleotide structures, whereupon a dependence of the stability on field strength emerges. An explicit calculation for a co-operative transition of the DNA melting type is presented, and it is concluded that for sufficiently low ionic strengths, a field of the order of 10 kV/cm may be able to induce melting by lowering the Tm by a few degrees. The threshold effect found experimentally by Pörschke, and particularly the observed linear dependence of the threshold field on the logarithm of the ionic strength, appears here as a simple consequence of the linear increase of the stabilization free energy with the logarithm of ionic strength.
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