Synthetic peptide receptors applications

Bioassays, receptor assays, and immunoassays are used to measure GH. ° Most bioassays assess GH activity by analyzing a variety of growth-related metabohc changes in hypophysectomized rats or in cell cultures. A relatively simple and convenient bioassay, the Nb2 cell assay, uses cultures of GH-sensitive rat lymphoma cells.These bioassays are used primarily for calibrating GH reference materials or for comparing the biological potency and immunoreactivity of GH fragments and synthetic peptides. Receptor assays have also been applied to the measurement of GH, but their use has been limited to research applications. 

In addition to the three main types of immunological products that are widely available, more specialized preparations include synthetic peptide immune response modifiers such as those used to block T-cell responses in multiple sclerosis labelled monoclonal antibodies for cancer therapy or diagnosis and hybrid toxins containing a bacterial or plant toxin subunit attached to an antibody or human cell receptor-binding protein, and also intended mainly for cancer therapy. These have rather limited applications and for the most part, are designed to suppress or exploit the specificity of immune responses rather than to stimulate them. 

Much of the information gleaned from studies of ribonuclease S can be applied to studies of far more complex systems. In most cases the receptor-bound form of the peptide will not be known, but the same synthetic modeling approaches can be applied to probe the conformational features of the complex. Two recent examples of the application of this approach to the design of biologically active peptides will be considered in this section. 

Screening the encoded library produced interesting structures to build an SAR and to design focused libraries of binders for the artificial receptor, but some limitations of these linkers for applications different from peptide chemistry are clearly evident. The carbonate bond connecting the electrophone tag and the photocleavable linker (Figure 9.8) is sensitive to many organic reaction conditions, and the carboxylate requires an amino- or hydroxy function to be linked to the resin after each synthetic step to be encoded. 

Tlie basic study of intermolecular interactions is facihtated by one-bead-one-stRicture libraries which can be powerful tools for the discovery of hgands to synthetic receptors and vice versa. Encoded combinatorial libraries have been useful for disclosing ligands for well-designed macrocyclic host molecules and to elucidate their specificities for peptide sequences. These studies led via receptors with more flexibility to simple host molecules without elaborate design that ai e accessible to combinatorial synthesis. One application is the development of chemical sensors for analytes that are otherwise difficult to detect or only non-specificaUy detected. Such hbraries have been used to find new catalysts and enzyme mimics. 

---