Synthetic ligands

CP 55940 (79) and nabilone (80) are synthetic ligands for the cannabiaoid receptor. However, the identification of the eicosanoid, anandamide (81), as an endogenous cannabimimetic has provided an important tool to study cannabiaoid receptor function. 

Synthetic ligands Thiazolidinediones and some non-steroidal antiinflammatory drugs... 

Nature has created a diverse array of plant and animal toxins that act at mammalian muscle and ganglionic nAChRs or invertebrate nAChRs because the critical physiological functions of these receptors make them prime targets for defensive or predatory strategies. More recently, the perceived validity of neuronal nAChR as therapeutic targets has prompted the generation of new synthetic ligands. Examples are listed in Table 1. 

Table 4 summarizes the physiological functions of the PPAR isotypes and their synthetic ligands. 

PPAR isotype Tissues of highest expression Primary physiological effects Endogenous ligands Synthetic ligands Associated disease state/ indication... 

White, S., J.W. Szewczyk, J.M. Turner, E.E. Baird, and P.B. Dervan. Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands. Nature 1998, 393, 468-471. 

Synthetic ligands Morphine DPDPE U50488H None so far... 

To better understand the critical role of oligosaccharide-receptor interactions and their molecular mechanisms through the cluster-effect, and thus access optimized synthetic ligands, several research groups have shown creativity in proposing original multivalent platforms that could allow for tailored valencies, dimensions, and epitope orientations. 

Playle, R.C., D.G. Dixon, and K. Bumison. 1993a. Copper and cadmium binding to fish gills modification by dissolved organic carbon and synthetic ligands. Canad. Jour. Fish. Aquat. Sci. 50 2667-2677. 

In spite of the extensive homology in the key amino acids of the LBD (Fig. 1.3), each of the two ER isoforms has different affinities for natural and synthetic ligands (Table 1.1). This suggests that the responses are very different in tissues dominated by one or another receptor (Kuiper et al. 1996). 

Two examples of polycarbonyl and polyamino compounds are shown in Figure 5.7. Ethylenediaminetetraacetic add (EDTA) is a synthetic ligand. The other, a siderophore, is biologically derived. Other polycyclic structures that coordinate with iron are also common. 

Hussey SL (2002) Efficient delivery of streptavidin to mammalian cells clathrin-mediated endocytosis regulated by a synthetic ligand. J Am Chem Soc 124 6265-6273... 

P-CD was derivatized at the primary face with various synthetic ligands suitable to form ruthenium arene complexes. There is convincing spectroscopic evidence that the ruthenium complexes are formed and that lipophilic substrates bind into the cavity of P-CD. 

In conclusion it can be said, that micellar effects offer useful possibilities to tune the reactivity and separation characteristics of aqueous/organic biphasic hydroformylations. Nevertheless, the added sensitivity of the systems to small changes in process variables and the added cost of surfactants and/or specially synthetized ligands have to be justified by high added value products or on grounds of process cost savings. Whether this will happen on industrial scale (perhaps in the hydroformylation of higher olefins) remains to be seen. 

Sodium ISEs (especially for biological applications) contain monensin XXVII (see [98, 99, 107,203]). Synthetic ligands for sodium ISEs were gradually developed the latest type, XXVIII [64] has properties sufficient for the ISE to be comparable to the sodium glass electrode (see [91 ] for determination of Na in urine). 

The physiological hormone for the RARs is all-frans-retinoic acid RA 221 and that for the RXRs is its geometric isomer, 9-czs-retinoic acid (9-czs-RA 222) [320]. However, these polyolefinic hormones are of only limited use in elucidating the precise biological roles of each receptor family. Synthetic ligands that specifically activate only the RXR or RAR hormonal pathway and which cannot be converted into forms that activate the other pathway would be of much greater use in this regard. 

Figure 8. Natural, non-natural and synthetic ligands for ERft, PPARy, and FXR receptors.

More attention will be given to the AC s than to the AEC s. Furthermore, the discussion will bear principally on synthetic ligands. The very interesting natural antibiotic ligands have been discussed in other chapters (see pp. 86—96) their properties will be used here merely for illustration and comparison purposes since they are more difficult to analyze in terms of strategies because of their complicated structural features. 

The presently known synthetic ligands capable of forming stable and selective AC complexes are mostly neutral cyclic structures. They generally contain O and N binding sites and sometimes S sites. Most are of structural types D and G some E, H and J systems have also been obtained (Figure 2). 

In addition to the synthetic ligands described above, a number of natural (generally macrocyclic) substances also form stable AC and AEC complexes. Some relevant results will be used below for comparison purposes only, since they are treated in detail elsewhere in this volume (pp. 135 ff.). Before discussing the complexes themselves we consider briefly the structural properties of the free synthetic ligands. 

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