Ligand affinity kinetics

In order to elicit their effect, drug molecules must be bound to the cells of the effector organ. Binding commonly occurs at specific cell structures, namely, the receptors. The analysis of drug binding to receptors aims to determine the affinity of ligands, the kinetics of interaction, and the characteristics of the binding site itself. 

FIGURE 16.16 Selectins and their physiological ligands affinity and kinetics. 

Wild, M K, Huang, M.-C., Schulze-Horsel, U, van der Merwe, P A, Vestweber, D, Affinity, kinetics and thermodynamics of E-selectin binding to E-selectin ligand-1, J. Biol Chem., 276, 31602-31612, 2001. 

CEP receptors exhibit high ligand affinity and saturation kinetics for ligand binding. The protein portion of these complexes appears to participate in ligand-receptor interaction since protease treatment of aortic CEP complexes abolishes uptake [24]. Binding is competitively inhibited by polyanions in a pattern similar to the inhibition observed for the acetyl-LDL receptor [24]. However, the CEP receptor appears to be distinct from the acetyl-LDL receptor since their ligands do not mutually compete for uptake [24]. 

Both the AFM rupture experiments as well as our simulation studies focussed on the streptavidin-biotin complex as a model system for specific ligand binding. Streptavidin is a particularly well-studied protein and binds its ligand biotin with high affinity and specificity [51]. Whereas previous experiments (see references in Ref. [49]) and simulation studies [52] referred only to bound/unbound states and the associated kinetics, the recent AFM... 

The oxygen affinity of the derivative was shown to be about half that of unmodified hemoglobin under similar conditions, but a degree of cooperativity was preserved. Kquilihrium and kinetic ligand-binding studies on this derivative have been interpreted (62) to show a perturbed R state. It is beheved that although the reaction is between the two P-chains, aP-dimers function independentiy, probably through a flexible connection. 

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