Mixed Mode of Ligand-DNA Binding Results in S-Shaped Binding Curves

Abstract

S-shaped binding curves often characterize interactions of ligands with nucleic acid molecules as analyzed by different physico-chemical and biophysical techniques. S-shaped experimental binding curves are usually interpreted as indicative of the positive cooperative interactions between the bound ligand molecules. This paper demonstrates that S-shaped binding curves may occur as a result of the "mixed mode" of DNA binding by the same ligand molecule. Mixed mode of the ligand-DNA binding can occur, for example, due to 1) isomerization or dimerization of the ligands in solution or on the DNA lattice, 2) their ability to intercalate the DNA and to bind it within the minor groove in different orientations. DNA-ligand complexes are characterized by the length of the ligand binding site on the DNA lattice (so-called "multiple-contact" model). We show here that if two or more complexes with different lengths of the ligand binding sites could be produced by the same ligand, the dependence of the concentration of the complex with the shorter length of binding site on the total concentration of ligand should be S-shaped. Our theoretical model is confirmed by comparison of the calculated and experimental CD binding curves for bis-netropsin binding to poly(dA-dT) poly(dA-dT). Bis-netropsin forms two types of DNA complexes due to its ability to interact with the DNA as monomers and trimers. Experimental S-shaped bis-netropsin-DNA binding curve is shown to be in good correlation with those calculated on the basis of our theoretical model. The present work provides new insight into the analysis of ligand-DNA binding curves.

Isotherm of ligand adsorption on DNA at multiplicative noise

“…The second one is in the analysis of the experimental adsorption isotherms. It is well known that the analysis of adsorption provides some valuable information about the mechanism of ligand binding to DNA and, in particular, there exist several variants of interpretation of the S-form of the curve (Arakelyan, Haroutiunian, Abgaryan, Arakelyan, & Haroutunian, 2004;Nechipurenko, Mikheikin, Streltsov, Zasedatelev, & Nabiev, 2001). It is possible that in some experiments at small ligand concentrations in the solution, an adsorption on DNA is absent, and this circumstance might be the cause for the representation of the adsorption isotherm in an S-form curve.…”

Interaction of clinically important human DNA topoisomerase I poison, topotecan, with double‐stranded DNA

“…The S shape of trace 3 in Figure 7(A) presumes the formation of TPT‐DNA complexes of at least two types according to two qualitatively different binding models 26, 27. The first model presumes that the different TPT‐DNA complexes differ in binding constant values and in the length occupied by TPT on the DNA sequence 26, 27.…”

“…The first model presumes that the different TPT‐DNA complexes differ in binding constant values and in the length occupied by TPT on the DNA sequence 26, 27. In this case the FLD technique should preferably detect the complex where TPT exhibits a bigger binding constant and occupies a longer DNA sequence 26, 27. The second model suggests that an increase of the DNA concentration provokes a TPT‐mediated intermolecular DNA interaction.…”

Synthetic polycation: Polynucleotide interactions determined using liquid chromatography with short monolithic columns

“…2. It can be seen, that ionexchange chromatogram exhibit S-shape type of macrocation adsorption related to a multilayer polymer adsorption [21]. Such adsorption does not fit to Langmuir's equation usually used for calculations of q max and K diss .…”