Dependence of Concanavalin A Binding on Anomeric Configuration, Linkage Type, and Ligand Multiplicity for Thiourea-Bridged Mannopyranosyl–β-Cyclodextrin Conjugates

Probing Carbohydrate-Lectin Recognition in Heterogeneous Environments with Monodisperse Cyclodextrin-Based Glycoclusters

“…The concentration of glycoclusters required to achieve 50% inhibition, the IC 50 values (Table ) are assumed to be inversely proportional to the lectin-saccharide free energy of binding. For comparative purposes, they were normalized to the affinity shown by methyl α- d -mannopyranoside in a parallel experiment (IC 50 865 ± 30 μM) . In agreement with previous results, , a substantial amplification of Con A-HRP avidity was observed for conjugates where the mannosyl units were presented in triads, and little, if any, differences were noticed among mono- or dimannosylated dendrons, regardless of the presence or absence of other saccharidic or nonsaccharidic elements.…”

Probing Carbohydrate-Lectin Recognition in Heterogeneous Environments with Monodisperse Cyclodextrin-Based Glycoclusters

“…The concentration of glycoclusters required to achieve 50% inhibition, the IC 50 values (Table ) are assumed to be inversely proportional to the lectin-saccharide free energy of binding. For comparative purposes, they were normalized to the affinity shown by methyl α- d -mannopyranoside in a parallel experiment (IC 50 865 ± 30 μM) . In agreement with previous results, , a substantial amplification of Con A-HRP avidity was observed for conjugates where the mannosyl units were presented in triads, and little, if any, differences were noticed among mono- or dimannosylated dendrons, regardless of the presence or absence of other saccharidic or nonsaccharidic elements.…”

Optimizing Saccharide-Directed Molecular Delivery to Biological Receptors: Design, Synthesis, and Biological Evaluation of Glycodendrimer−Cyclodextrin Conjugates

“…The prepared cyclodextrin conjugates exhibited extremely high water solubilities, above 20-fold higher as compared to the parent βCD (15 mM). Moreover, docetaxel solubilization experiments in water showed solubility values similar to those obtained previously for monovalent CDs, significantly higher than those reported for per-(C-6)-substituted derivatives 11b. For instance, up to 4.5 and 4.7 g L -1 of Taxotère was solubilized in 25 mM aqueous solutions of 29 and 30 at 25 °C, respectively, that is, above 1000-fold solubility enhancements as compared to the water solubility of the drug (0.004 g L -1 ) 16a.…”

“…The corresponding IC 50 values for inhibition of Con A−yeast mannan binding (Table ) reflected the expected amplification of lectin-binding strength for the higher-valent representatives (up to 22-fold in a molar basis for hexavalent as compared to monovalent derivatives), indicative of a strong cluster effect . The Con A binding capacity of the monosubstituted hexavalent βCD conjugate 32 (IC 50 = 10 μM) actually surpassed that previously encountered for per-(C-6)-substituted βCD heptamannoside derivatives (IC 50 > 70 μM),11b thus illustrating the strong dependence of carbohydrate−lectin recognition processes upon the presentation mode of receptor-binding epitopes in multivalent ligands . Notwithstanding, virtually no difference in binding efficiency was detected between mono- and divalent or between tri- and tetravalent ligands.…”

Carbohydrate Microarrays

“…A direct application of the method would be the rapid diagnosis of infectious diseases. [16] In any case, probing of microspotted slides containing appropriately tethered N-acetyl-D-glucosamine, lactose, maltose, and cellobiose ligands with FITC-tagged lectins showed a binding pattern identical to that in solution ( Figure 2); this demonstrates that microarrays prepared by this technique allow thousands of carbohydrate ± protein binding assays (up to 12 000 microspots in this work) to be performed in a parallel fashion. More robust immobilization techniques may be necessary for those channels, especially when low-molecularweight recognition epitopes are involved.…”

Probing Carbohydrate-Lectin Recognition in Heterogeneous Environments with Monodisperse Cyclodextrin-Based Glycoclusters

“…The concentration of glycoclusters required to achieve 50% inhibition, the IC 50 values (Table ) are assumed to be inversely proportional to the lectin-saccharide free energy of binding. For comparative purposes, they were normalized to the affinity shown by methyl α- d -mannopyranoside in a parallel experiment (IC 50 865 ± 30 μM) . In agreement with previous results, , a substantial amplification of Con A-HRP avidity was observed for conjugates where the mannosyl units were presented in triads, and little, if any, differences were noticed among mono- or dimannosylated dendrons, regardless of the presence or absence of other saccharidic or nonsaccharidic elements.…”

Optimizing Saccharide-Directed Molecular Delivery to Biological Receptors: Design, Synthesis, and Biological Evaluation of Glycodendrimer−Cyclodextrin Conjugates

“…The prepared cyclodextrin conjugates exhibited extremely high water solubilities, above 20-fold higher as compared to the parent βCD (15 mM). Moreover, docetaxel solubilization experiments in water showed solubility values similar to those obtained previously for monovalent CDs, significantly higher than those reported for per-(C-6)-substituted derivatives 11b. For instance, up to 4.5 and 4.7 g L -1 of Taxotère was solubilized in 25 mM aqueous solutions of 29 and 30 at 25 °C, respectively, that is, above 1000-fold solubility enhancements as compared to the water solubility of the drug (0.004 g L -1 ) 16a.…”

“…The corresponding IC 50 values for inhibition of Con A−yeast mannan binding (Table ) reflected the expected amplification of lectin-binding strength for the higher-valent representatives (up to 22-fold in a molar basis for hexavalent as compared to monovalent derivatives), indicative of a strong cluster effect . The Con A binding capacity of the monosubstituted hexavalent βCD conjugate 32 (IC 50 = 10 μM) actually surpassed that previously encountered for per-(C-6)-substituted βCD heptamannoside derivatives (IC 50 > 70 μM),11b thus illustrating the strong dependence of carbohydrate−lectin recognition processes upon the presentation mode of receptor-binding epitopes in multivalent ligands . Notwithstanding, virtually no difference in binding efficiency was detected between mono- and divalent or between tri- and tetravalent ligands.…”

Carbohydrate Microarrays

“…A direct application of the method would be the rapid diagnosis of infectious diseases. [16] In any case, probing of microspotted slides containing appropriately tethered N-acetyl-D-glucosamine, lactose, maltose, and cellobiose ligands with FITC-tagged lectins showed a binding pattern identical to that in solution ( Figure 2); this demonstrates that microarrays prepared by this technique allow thousands of carbohydrate ± protein binding assays (up to 12 000 microspots in this work) to be performed in a parallel fashion. More robust immobilization techniques may be necessary for those channels, especially when low-molecularweight recognition epitopes are involved.…”

Probing Carbohydrate-Lectin Recognition in Heterogeneous Environments with Monodisperse Cyclodextrin-Based Glycoclusters

“…The concentration of glycoclusters required to achieve 50% inhibition, the IC 50 values (Table ) are assumed to be inversely proportional to the lectin-saccharide free energy of binding. For comparative purposes, they were normalized to the affinity shown by methyl α- d -mannopyranoside in a parallel experiment (IC 50 865 ± 30 μM) . In agreement with previous results, , a substantial amplification of Con A-HRP avidity was observed for conjugates where the mannosyl units were presented in triads, and little, if any, differences were noticed among mono- or dimannosylated dendrons, regardless of the presence or absence of other saccharidic or nonsaccharidic elements.…”

Optimizing Saccharide-Directed Molecular Delivery to Biological Receptors: Design, Synthesis, and Biological Evaluation of Glycodendrimer−Cyclodextrin Conjugates

“…The prepared cyclodextrin conjugates exhibited extremely high water solubilities, above 20-fold higher as compared to the parent βCD (15 mM). Moreover, docetaxel solubilization experiments in water showed solubility values similar to those obtained previously for monovalent CDs, significantly higher than those reported for per-(C-6)-substituted derivatives 11b. For instance, up to 4.5 and 4.7 g L -1 of Taxotère was solubilized in 25 mM aqueous solutions of 29 and 30 at 25 °C, respectively, that is, above 1000-fold solubility enhancements as compared to the water solubility of the drug (0.004 g L -1 ) 16a.…”

“…The corresponding IC 50 values for inhibition of Con A−yeast mannan binding (Table ) reflected the expected amplification of lectin-binding strength for the higher-valent representatives (up to 22-fold in a molar basis for hexavalent as compared to monovalent derivatives), indicative of a strong cluster effect . The Con A binding capacity of the monosubstituted hexavalent βCD conjugate 32 (IC 50 = 10 μM) actually surpassed that previously encountered for per-(C-6)-substituted βCD heptamannoside derivatives (IC 50 > 70 μM),11b thus illustrating the strong dependence of carbohydrate−lectin recognition processes upon the presentation mode of receptor-binding epitopes in multivalent ligands . Notwithstanding, virtually no difference in binding efficiency was detected between mono- and divalent or between tri- and tetravalent ligands.…”

Carbohydrate Microarrays

“…A direct application of the method would be the rapid diagnosis of infectious diseases. [16] In any case, probing of microspotted slides containing appropriately tethered N-acetyl-D-glucosamine, lactose, maltose, and cellobiose ligands with FITC-tagged lectins showed a binding pattern identical to that in solution ( Figure 2); this demonstrates that microarrays prepared by this technique allow thousands of carbohydrate ± protein binding assays (up to 12 000 microspots in this work) to be performed in a parallel fashion. More robust immobilization techniques may be necessary for those channels, especially when low-molecularweight recognition epitopes are involved.…”