Ligand affinity receptor protein, binding site

The selection of building blocks is based on information derived from, for example, computational chemistry, where potential virtual ligand molecules are modeled to fit the receptor-protein binding site. Combinatorial chemistry commences with a scaffold or framework to which additional groups are added to improve the binding affinity. Compounds are prepared and later screened using HTS. In this way, many compounds are tested within a short time frame to speed up drug discovery. 

Saturation binding, a biochemical procedure that quantifies the amount of traceable ligand (i.e., radioligand) to a receptor protein. It yields the affinity of the ligand and the maximal number of binding sites (i)max) see Chapter 4.2.1. 

It seems clear that complexes 28 and 29 both enter cancer cells by transferrin-mediation. Tumor cells are known to have a high density of transferrin receptors, and this provides a route for the uptake of ruthenium (175). In normal blood plasma, transferrin is only one-third saturated with Fe(III) and therefore vacant sites are available for Ru(III) binding. Baker et al. have shown by X-ray crystallography that complex 29 binds to His-253 of apolactoferrin, one of the Fe(III) ligands in the iron binding cleft of the N-lobe, with displacement of a chloride ligand (176). Ruthenium(III) is well known to have a high affinity for solvent-exposed His side chains of proteins (177). Complex... 

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