Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts

Biotin[6]uril Esters: Chloride-Selective Transmembrane Anion Carriers Employing C-H···Anion Interactions.

Biotin[6]uril hexaesters represent a new class of anionophores which operate solely through C-H···anion interactions. The use of soft H-bond donors favors the transport of less hydrophilic anions (e.g. Cl(-), NO3(-)) over hard, stongly hydrated anions (e.g. HCO3(-) and SO4(2-)). Especially relevant is the selectivity between chloride and bicarbonate, the major inorganic anions in biological systems.info:eu-repo/semantics/publishe

Entropy/enthalpy compensation in anion binding:Biotin[6]uril and biotin-L-sulfoxide[6]uril reveal strong solvent dependency

Binding of anions using macrocyclic structures with a nonpolar interior using the CH···anion interaction as the recognition motif has gained popularity in the past few years, and such receptors often rely on a subtle interplay between enthalpic and entropic factors. For these types of receptors solvation of both the anion and the binding pocket of the macrocyclic host play important roles in the overall energetic picture of the binding event. Systematic chemical modifications of synthetic receptors that are able to bind anions in a variety of solvents is an important tool to gain understanding of the factors that determine the supramolecular chemistry of anions. Here we present the chiral macrocyclic structure biotin-l-sulfoxide­[6]­uril as a host molecule that binds anions in both water and in organic solvents. Biotin-l-sulfoxide­[6]­uril is prepared in a highly diastereoselective one-pot synthesis from the macrocycle biotin[6]­uril. We compare the binding properties with that of biotin[6]­uril, also studied in acetonitrile and in aqueous buffer at neutral pH. The biotin-l-sulfoxide­[6]­uril generally exhibits stronger recognition of anions in acetonitrile, but weaker binding in water as compared to the biotin[6]­uril macrocycle. We have studied the binding events using a combination of NMR spectroscopy, isothermal titration calorimetry (ITC), and computational methods

Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts