Receptor sites, hypothetical

Figure 2-18 Diagram of a hypothetical receptor site, showing distances between functional groups.

On the basis of these and other studies Bentley and his colleagues5,6 have proposed a hypothetical receptor site (V) which will accommodate these new molecules as well as the older analgesic structures... 

Fig. (7). A model for the binding of emetine-lype agonist to the hypothetical receptor site...

The hypothetical enantiophore queries are constructed from the CSP receptor interaction sites as listed above. They are defined in terms of geometric objects (points, lines, planes, centroids, normal vectors) and constraints (distances, angles, dihedral angles, exclusion sphere) which are directly inferred from projected CSP receptor-site points. For instance, the enantiophore in Fig. 4-7 contains three point attachments obtained by ... 

Consider the two hypothetical situations illustrated in Figure 2. On the top is pictured a collection of individual fluorescent receptors, while on the bottom is pictured the same number of receptors, yet they are connected via a molecular wire conjugated polymer. In addition, suppose it is known that binding of the analyte paraquat (PQ) into a receptor causes a complete quenching ofits fluorescence. In the case of individual receptors, the binding of one analyte gives only a small diminution in the total intensity of emission observed. This is because each exciton is fixed on one molecule and cannot communicate with other receptor sites. 

The fundamental neurobiological importance of the GABA A receptor is underscored by observations that even more receptor sites exist at or near this complex (Fig. 8—20). This includes receptor sites for nonbenzodiazepine sedative-hypnotics such as zolpidem and zaleplon, for the convulsant drug picrotoxin, for the anticonvulsant barbiturates, and perhaps even for alcohol. This receptor complex is hypothetically responsible in part for mediating such wide-ranging CNS activities as seizures, anticonvulsant drug effects, and the behavioral effects of alcohol, as well as the known anxiolytic, sedative-hypnotic, and muscle relaxant effects of the benzodiazepines. 

Flg 2 (a) Hypothetical receptor map of the active site of prostaglandin cyclooxygenase, showing points of binding or reactivity with the enzyme substrate, arachidonic acid (b) The anti-inflammatory aryl-acetlc acids - here, Indomethacln - which inhibit this enzyme, can fit the same receptor map in a way which explains their structure-activity relationships (from Ref 13 with permission) ... 

The Squibb team also worked back from their conception of the receptor s shape, based on their knowledge of details of the cleavage reaction it performed. Since the ACE protein had not itself been structurally defined, they developed a hypothetical model based on the active site of another enzyme that performed a similar cleavage reaction, and whose structure was known from x-ray crystallography. The research team crafted compounds to fit into the hypothetical active site of ACE and discovered a compound with inhibitory activity that was similar in shape to two amino-acids in tandem. They performed further chemical modifications of this molecule and eventually found a chemical amenable to oral administration that was 1,000 times more potent than their initial lead molecule. The synthetic drug had greater activity than the nine-amino-acid venom peptide. 

Molluscicidal activity of anacardic acids, notably of the 8Z,1 lZ,14-triene has been reported [276] and the mechanism of its action has been studied by examining its role in initiating the action of prostacyclin (PGI2) in human blood platelets through competition for receptor sites although the connectioin between the two systems may be hypothetical. More recently the molluscicidal of anacardic acids and its complexes with copper II and lead has been investigated [277]. 

Fig. 8. Hypothetical binding sites between (a) GAj and the dwarf pea receptor (b) GA, and the cucumber receptor . I=obligatory binding sites II=anciUary binding sites III=hydrophobic interaction site IV electrostatic interaction site. (Reprinted with permission from Serebryakov et al.. Phytochemistry 23, 1847 1984. Copyright 1984 Pergamon Press Ltd.)...

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