Receptor-ligand mimetics

Previous reviews on peptidomimetics have addressed pseudopeptides (11), macrocyclic mimetics (13), natural product mimetics (14), cyclic protease inhibitors (15), mimetics for receptor ligands (16-22), and earlier general overviews (23-29). This review will focus on the design process itself. Novel peptidomimetics in which the structural relationship between parent peptide and the peptidomimetic has been established by biophysical methods are used to clarify the principles. Successful approaches are highlighted to illustrate how these concepts are currently used. 

The design of assay systems is another particularly important factor for testing the sample compounds. Assays have to be specific and sensitive. The assays used for HTS come in many forms. There are binding assays, or enzyme-based or cell-based assays. Cell-based assays have become an important test compared with other in vitro assays, as they can provide information about bioavailability, cytotoxicity and effects on biochemical pathway. Invariably, the enzyme-based and cell-based assay systems consist of receptors or mimetics of receptors (components that mimic active parts of receptors). Normally the assays are linked to an indicator that shows the ligand-receptor interaction as some forms of signal. Radioligand binding... 

These initial reports showed that functional carbohydrate-mimetic peptides could be found. These peptides acted as ligands for several biologically important proteins, and had potential in the development of therapeutics. Subsequently, peptides that act as molecular mimics of carbohydrates in binding to a wide variety of different receptors have been identified [ 14-44] these are summarized in Table 1 and reviewed in [ 13]. Some of these peptides were able not only to bind to a particular receptor, but also to act as immunologically functional mimics and to induce an anti-carbohydrate immune re-... 

Alternatively, binding affinity between the mimetic ligand and receptor might be achieved by a different mechanism than that of the natural ligand. The mimetic ligand might contact a different area of the receptor binding site, or provide a different set of intermolecular interactions. As shown in... 

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