Receptors with Different Binding Sites

In this section, we discuss macrocyclic receptors prepared specifically with the aim of producing molecules with different binding motifs. Such systems, which will be considered mostly in the context of binding anions with multiple protonation sites (e.g., phosphates or sulfates) in solution, can be considered as a subset of the large class of compounds known as ditopic receptors. 

A noteworthy finding emerging from these detailed studies was that the monotopic cyclopeptide 44 actually proved to be a more efficient receptor for sulfate anions than the ditopic system 45 (for 44, AH = 19.3kJ/mol and logKT = 6.48 in 50% D20/CH30H, where / , = K n-K.l2 M 2 ). Furthermore, in contrast with the design expectations, microcalorimetric titrations (e.g., ITC analyses) revealed that sulfate is bound to receptor 45 with a 2 1 binding stoichiometry. 

Such intriguing findings provide support for the notion that the right spacer group can significantly increase the binding affinity of a given type of ditopic receptor. 

Shinkai and coworkers have reported that a combination of both allosteric and hydrogen-bonding interactions with anions was achieved by the bicydic host 50 

Pyrroles are good hydrogen-bond donors and, subject to appropriate caveats, are relatively insensitive to either protonation or deprotonation effects. Therefore, they have seen increasing use in the construction of highly efficient anion receptors [18], as well as more recently in the construction of hybrid receptors. An example of a pyrrole-containing hybrid receptor that was reported quite recently is compound 51 

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In comparison to artificial receptors with concave binding sites (see section 2) the membrane gaps provide the advantage of a much larger size. Depending on the height of the membrane at least three to five different molecules can be placed in variable order. Furthermore analysis by cyclic voltammetry is easy and the self-assembled systems can be prepared easily on a large scale if colloidal particles are used as subphase. 

The complex between GH and GHR contains one molecule of the hormone and two molecules of the receptor, even though the hormone does not have a pseudosymmetric structure with two similar binding sites. Instead, there are two completely different binding sites on the hormone, each of which binds to similar sites on the receptor molecules. These interactions are so far unique. 

FIG U RE 65.2 Schematic model of the GABAa receptor. The receptor spans the cell membrane. GABA binds to the outside of the receptor, causing an influx of Cl ions through the channel. Benzodiazepines and barbiturates interact with different recognition sites on the receptor and increase the effectiveness of GABA. 

The bioactivity of a drug is the result of interaction with a biological receptor, a protein molecule with a binding site that is also chiral and stereospecific. The interaction of the D isomer of a drug with a chiral receptor site will differ from the interaction of the L isomer with that site. 

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