Crystal structure of a complex between β-glucopyranose and a macrocyclic receptor with dendritic multicharged water solubilizing chains

International audienceUsing commercial screens for crystallization of biomolecules and taking advantage of the use of racemic crystallography allowed the production of x-ray quality single crystals and the elucidation at 1.08 Å resolution of the solid state structure of a difficult target: the complex between glucopyranose and a water soluble macrocyclic receptor equipped with dendritic multianionic solubilizing chains

Affinity enhancement by dendritic side chains in synthetic carbohydrate receptors

Dendritic side chains have been used to modify the binding environment in anthracene-based synthetic carbohydrate receptors. Control of length, charge, and branching enabled the positioning of side-chain carboxylate groups in such a way that they assisted in binding substrates rather than blocking the cavity. Conformational degeneracy in the dendrimers resulted in effective preorganization despite the flexibility of the system. Strong binding was observed to glucosammonium ions in water, with K(a) values up to 7000 m(−1). Affinities for uncharged substrates (glucose and N-acetylglucosamine) were also enhanced, despite competition from solvent and the absence of electrostatic interactions

Rapid Macrocycle Threading by a Fluorescent Dye–Polymer Conjugate in Water with Nanomolar Affinity

A macrocyclic tetralactam host is threaded by a highly fluorescent squaraine dye that is flanked by two polyethylene glycol (PEG) chains with nanomolar dissociation constants in water. Furthermore, the rates of bimolecular association are very fast with <i>k</i>_on ≈ 10⁶–10⁷ M^–1 s^–1. The association is effective under cell culture conditions and produces large changes in dye optical properties including turn-on near-infrared fluorescence that can be imaged using cell microscopy. Association constants in water are ∼1000 times higher than those in organic solvents and strongly enthalpically favored at 27 °C. The threading rate is hardly affected by the length of the PEG chains that flank the squaraine dye. For example, macrocycle threading by a dye conjugate with two appended PEG2000 chains is only three times slower than threading by a conjugate with triethylene glycol chains that are 20 times shorter. The results are a promising advance toward synthetic mimics of streptavidin/biotin