Ligand-receptor relationships

Chemokines exhibit complex ligand-receptor relationships. Often, individual chemokines can bind productively to more than one receptor, and many chemokine receptors can signal in response to more than one chemokine. Usually, these chemokine receptors bind multiple chemokines within the same subfamily. The best documented example of chemokine receptor promiscuity across subfamilies involves CXCR3 binding to CCL21. 

This is a linear relation often referred to as the Cheng-Prusoff relationship [5], It is characteristic of competitive ligand-receptor interactions. An example is shown in Figure 4.6b. 

Fuentes, J.A. (2005) Synthesis and structure-activity relationships of a new model of arylpiperazines. 8. Computational simulation of ligand-receptor interaction of 5-HT(lA)R agonists with selectivity over alphal-adrenoceptors. Journal of Medicinal Chemistry, 48, 2548-2558. 

Some of the best understood polyvalent interactions are found in immune and host defense systems as well as ligand-receptor activation. An example is the use of a polyvalent immunogen based on a synthetic peptide to elicit immune responses. The subsequent production of site-specific antibodies can then be employed to confirm the identity of proteins derived from recombinant DNA, to explore biosynthetic pathways, to define precursor-product relationships (e.g., proenzyme and preproenzyme), and to determine protein structural domains.19 ... 

For the pharmacophore-based screening, a 3-D-pharmaco-phore feature is constmcted by structure-activity relationship analysis on a series of active componnds (26) or is dednced from the X-ray crystal stmcture of a ligand-receptor complex (27). Taking this 3-D-pharmacophore feature as a query structure, 3-D database search can be performed to select the molecnles from the available chemical databases, which contain the pharmacophore elements and may conform to the pharmacophore geometric constraints. Then the selected compounds are obtained either from commercial sonrces or from organic synthesis for the real pharmacologic assays (see Fig. 3). 

To enhance our understanding of ligand-receptor interactions and bring coherence to these relationships, there needs to be a con-... 

Hirokawa S, Imasaka T, Imasaka T. Chlorine substitution pattern, molecular electronic properties, and the nature of the ligand-receptor interaction Quantitative property-activity relationships of polychlorinated dibenzofurans. Chem Res Toxicol 2005 18 232-8. 

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