Binding constant association

Figure 31 Scheme for the protein-binding, diffusional, and partitioning processes and barriers that are encountered by a highly lipophilic and membrane-interactive drug (D) as it permeates through a cell within a continuous monolayer, h and h, thicknesses of the aqueous boundary layers. kd and ka, dissociation and association binding constants, respectively. P, protein molecule. Permeability coefficients Effective, Pe aqueous boundary layer, PABL and PW apical membrane, Pap basolateral membrane, Pbl. 

Again, the statistical factors 4, 5, etc., arise because Xr and K-y are intrinsic association binding constants, yet the overall expressions for the complexes requires extrinsic parameters e.g., Kr = [RX]/[R][X] = [R4X2]/[R4X][X] because there are three unfilled sites in the R4X molecule and two in each R4X2 molecule (see also Example 9.12). The fractional saturation Y is again defined by Eq. (9.49) ... 

Aida et al. noticed that zinc porphyrin (ZnP) cyclic dimer formed an inclusion complex with Cgo, stable enough to remain associated even under chromatographic conditions. The cyclic dimer model was further extensively studied to improve the association binding constants and thus the selectivity with fullerenes. An exhaustive report of this work has been published recently. ... 

While a number of proteins have been crystallized in this manner, the majority of studies have focused on a robust system comprising the tetrameric protein streptavidin and the vitamin biotin. The choice of this system is primcirily motivated by the strong bond between biotin and streptavidin (having an association equilibrium constant, Ka Tbe binding properties were recently... 

Chaput, Jeminet and Juillard measured the association constants of several simple polyethylene glycols with Na", K", Cs", and Tl". Phase transfer catalytic processes and most biological processes are more likely to involve the first two cations rather than the latter two, so we will confine the discussion to these. Stability constants for the dimethyl ethers of tetra-, penta-, hexa-, and heptaethylene glycols were determined poten-tiometrically in anhydrous methanol solution and are shown in Table 7.1. In the third column of the table, the ratio of binding constants (Ks/K s) is calculated. Note that Simon and his coworkers have referred to this ratio as the selectivity constant. ... 

The equilibrium binding constant for this 1 1 association is Xu = ki/lLi. The Xu values were measured spectrophotometrically, and the rate constants were determined by the T-jump method (independently of the X,j values), except for substrate No. 6, which could be studied by a conventional mixing technique. Perhaps the most striking feature of these data is the great variability of the rate constants with structure compared with the relative insensitivity of the equilibrium constants. This can be accounted for if the substrate must undergo desolvation before it enters the ligand cavity and then is largely resolvated in the final inclusion complex. ... 

The data in the upper and lower panels were fit simultaneously with a single association rate constant (k = 3.23 x lO s ) and separate dissociation rate constants (k = 0.0108/s, upper panel 0.083/s, lower panel). The kinetic aspects of the fit were verified by the agreement with the equilibrium binding (see Figure 4 caption). 

Here, binding is regarded as a bimolecular reaction and k+l and are, respectively, the association rate constant (M 1 s-1) and the dissociation rate constant (s-1). 

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