Conformational of ligands

Due to the fact that cross-correlated relaxation depends linearly on the correlation time, it can be used to determine the conformation of ligands when bound to target molecules, provided that the off rate is fast enough to enable detection of the cross-correlated relaxation rate via the free ligand [33, 34]. The conditions under which such an experiment can be performed are similar to those found for transferred NOEs [35], and, for Kd values... 

The strategy used to design active and selective catalysts was based on the following five factors for regulation, (i) conformation of ligands coordinated to Rh atom (ii) orientation of a vacant site on Rh (iii) cavity with the template molecular shape for reaction space produced behind template removal (iv) architecture of the cavity wall and (v) micropore in inorganic polymer-matrix overlayers stabilizing the active species at the surface [46, 47, 71]. 

Most of the fluoro derivatives of proline described in the literature are fluorinated in the 4 position. 4-Fluoroprolines are able to mimic 4-hydroxyproline, present in some proteins and polypeptides. On the other hand, 4-fluorination could suppress oxidative metabolism or modified ring conformation of ligands.The labeled analogues may be used as probes in PET (positron emission tomography) for localization of tumors... 

There are three NMR-based approaches suitable to propose the bioactive conformation of ligands in the absence of the coordinates of the whole complex 1. conformation analysis of free ligand in solution has a high chance to find with some population the bound conformation, although it may be solvent dependent (refer to Sect. 2.2.2) 2. determination of bound ligand conformation by means of transferred NMR methods if the dissociation constant is not smaller than approximately 50 pM (refer to Sects. 2.1 and 2.3) 3. solid-state NMR of the complex if the ligand can be obtained with 13C labels (Sect. 2.2.3). 

In addition to its application as a tool for determining bound conformations of ligands, this method has also been used recently as a screening aid for the identification from mixtures of ligands that bind to a protein of interest. This application is addressed in more detail in Section 3.3. 

In approaching the design of a chiral catalyst, the first question was whether or not our computational approach would allow us to predict the conformation of ligands around the Rh-Rh core. In particular, it seemed important to us, if we... 

Early attempts to map the properties of an unknown receptor (or any other ligand binding site) started from qualitative structure-activity relationships [878], from MO calculations of preferred conformations of ligands [879] and from the interpretation of multiparameter Hansch equations (e.g. Figure 48) [28]. 

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