Binding affinity, /?-CyDs

Various modified CyDs have been prepared to improve their binding affinities and selectivities controlled by external factors such as photons, metal ions, or pH. Such CyDs can act as chemosensors, artificial enzymes, drug carriers, or reaction fields. CyDs have been used as scaffolds for highly preorganizing functional units. There are aheady many reviews on modified CyDs [1-6, 8, 9, 123-125], so here we summarize only developments reported in the last seven years. 

Glucopyranose units of CyDs were converted to other pyranose units. A CyD analogue with six 3,6-anhydroglucose units and a 6-amino-glucopyranose unit was synthesized (67) [176]. This analogue had binding affinity for metal ions with Cs selectivity. 

CyDs were coupled with calixarene or crown ether to improve their binding affinity. j8-CyD functionalized with diaza-18-crown-6 at the primary face 68 showed 7-10-fold greater affinities for aromatic ammonium ions [178] and the introduction of a benzo-18-crown-6 moiety at the secondary-hydroxy side 69 improved chiral recognition for tryptophan (Trp), whereas its introduction at the primary-hydroxy side 70 was not effective for the Trp recognition [179]. 

Chen and coworkers [88] developed a rather involved extended MM model to analyze CyD binding affinities in terms of free energy, enthalpy, and entropy terms for benzene, resorcinol, and three drugs. They compared their calculated results for the native CyDs with the average solid state geometry and their calculated AG°... 

Figure 5 shows the release profiles of FP and its complexes from Witepsol H-15 suppositories. It is evident that the release rate of FP was significantly improved by the inclusion complexations with g-and DM-3-CyDs, while that from TM 3 CyD complex was almost the same as FP alone. The different release behavior between the three complexes may be attributed to the difference in dissolution rate and binding affinity of the complexes to the hydrophobic suppository base. In fact, the release rate of FP from hydrophilic bases such as macrogol suppositories containing the DM-3-CyD and TM-3-CyD complexes, was greater than that from hydrophobic bases such as Witepsol H-15 (11). 

CyD dimers and trimers have been developed to improve the binding ability for specific applications. Although the dimer linked with a short alkyl chain 1 showed higher affinity for ditopic guest molecules like p-toluidino-6-naphthalene sulfonate... 

Heptakis-6-(2-hydroxyethylamino)-6-deoxy-)S-CyD 28 can be used as an inhibitor of phosphate ester hydrolysis catalyzed by /l-protein phosphatase and add phosphatase, because 28 can bind to phosphotyrosine 29 and other aryl phosphate esters with significant affinity [147]. 

Guanidinium-appended j8-CyD was also prepared for the complexation of phosphates (e.g. 32) [148, 149). A,D-bisammonium-appended or A,D-bisguanidinium-appended yS-CyD (30 and 31, respectively) displayed significantly enhanced binding of phosphotyrosine, whereas monoammonium-appended fi-CyD showed low affinity and monoguanidinium-appended f-CyD showed no detectable binding [149]. 

Crown ether-capped jS-CyD 71 showed a binding afEnity for 8-anilino-l-naphthalenesulfonate (AN S) 88 times higher than the native j8-CyD, but the affinity for Acridine Red and Rhodamine B was lower than that of the native 8-CyD... 

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