Macromolecule-ligand complexes

We will defer describing an example of an NMR determination of a macromolecule-ligand complex until Section 4.3, as part of a more general overview of DHFR-ligand complexes, but it suffices to say that there are now many examples in the literature of macromolecule-ligand complexes and some of these have recently been reviewed.2... 

The ring flipping of the trimethoxy aromatic ring mentioned above is manifest in the spectra shown in Fig. 27. The presence of such dynamic processes involving the ligand appear to be not uncommon in macromolecule-ligand complexes and the ability of NMR methods to detect such phenomena... 

In the context of this chapter structure-based design refers to the process of determining the three-dimensional structure of a lead molecule or macromolecular target, or determining the structure of the macromolecule-ligand complex, and using this information to... 

Figure 12.14. Schematic illustration of the effects of slow, intermediate, and fast exchange on the appearance of peaks in NMR spectra of macromolecule-ligand complexes. In the slow exchange case separate peaks are seen for free and bound forms. Note the broader peak for the bound ligand because it now adopts the correlation time of the macromolecule. In the fast...

Data are collected from the macromolecule-ligand complex crystals as for any other crystal and processed in the usual ways. The complex crystal data set, however, must be placed on a common numerical scale with the native crystal data so that relative differences between individual reflections can be formed by subtraction of the two. This is relatively straightforward since the differences introduced by the ligand are generally randomly distributed, and for the purpose of scaling, the two data sets can be assumed to have been produced from the same crystal. The residual after scaling and difference formation is... 

As the macromolecule-ligand complex leaves the column, a void of ligand is created until a new equilibrium is reached. This phenomenon was first observed by Hummel and Dreyer in 1962. In the chromatogram, as shown in Figure 13.7, the peak represents the excess of I (i.e., the amount of I in equilibrium with MI ) whereas the trough represents the deficiency of I (the concentration of I that binds to the macromolecule). The mean number of moles of bound ligands per mole of macromolecules f can be evaluated directly from the chromatogram. There are two techniques for the evaluation of f external calibration and internal calibration (Sun et al., 1984, 1985, 1993). 

Table 8 may serve as a powerful database for various purposes [94D1] estimates of V and v values required for molar mass determinations of macromolecules and macromolecule-ligand complexes (e.g., in ultracentrifugal and solution scattering studies) estimation of the contribution of specific and unspecific... 

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