Ligands, solution conformation

Ligand Solution conformation Charge/tautomeric state Solution dynamics Bound conformation Pharmacophore models 1D/2D NMR Chemical shift Line shape/relaxation analysis TrNOE All of the above, including 1D/2D of multiple ligands... 

II. Ligand-Based Investigations A The Solution Conformation of Bradykinin... 

Behaviour of this type is typified by the co-ordination of a ligand such as 2,2 -bipyri-dine. The equilibrium solution conformation of the ligand is trans-coplanar, although there is free rotation about the interannular C-C bond, whereas in its metal complexes it usually behaves as a chelating didentate species, and, thus, adopts the m-coplanar conformation (Fig. 2-4). 

The simplest experiments are those that focus just on the ligand. These are typically used to determine solution conformations or 3D structures of ligands. Homonuclear1H II ) or 21) NMR experiments are used mainly here. At the other end of the scale, experiments to study the macromolecular binding partner often require labeled protein and multidimensional NMR methods, as indicated on the right-hand side of Fig. 1. Finally, many NMR experiments provide information... 

Fig. 8. Schematic representation of the trNOE effect. On the left the conformation of the unbound ligand does not allow the buildup of a NOE because the two protons are too far away. In the middle representation the bound conformation orients the two protons at a distance that allows the buildup of a NOE. After dissociation of the complex the information of spatial proximity of the two protons in the bound conformation is transferred back into the solution conformation (right), where the NOE still is observable.

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