Recognition and protection of glycosphingolipids by synthetic nanoparticle receptors.

Nanoparticle receptors were synthesized through micellar imprinting to bind glycosphingolipids with 20-140 µM binding affinities, meanwhile distinguishing glycan composition, the number of acyl chains, and hydroxylation of acyl chains in the lipids. The strong binding enabled the receptors to protect their target glycolipids dispersed in lipid membranes from enzymatic degradation.

Intrinsic Hydrophobicity versus Intraguest Interactions in Hydrophobically Driven Molecular Recognition in Water.

Molecular recognition of water-soluble molecules is challenging but can be achieved if the receptor possesses a hydrophobic binding interface complementary to the guest. When the guest molecule contains more than one hydrophobic group, intrahost interactions between the hydrophobes could strongly influence the binding of the guest by its host. In a series of ornithine derivatives functionalized with aromatic hydrophobes, the most electron-rich compound displayed the strongest binding, despite its lowest intrinsic hydrophobicity.

Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding.

A general method for sequence-specific binding of peptides remains elusive despite decades of research. By creating an array of "hydrophobically coded dimples" on the surface of surface-core doubly cross-linked micelles, we synthesized water-soluble nanoparticle receptors to recognize peptides by the location, number, and nature of their hydrophobic side chains. Minute differences in the side chains could be distinguished, and affinities up to 20 nM were obtained for biologically active oligopeptides in water.

A General Method for Selective Recognition of Monosaccharides and Oligosaccharides in Water.

Molecular recognition of carbohydrates plays vital roles in biology but has been difficult to achieve with synthetic receptors. Through covalent imprinting of carbohydrates in boroxole-functionalized cross-linked micelles, we prepared nanoparticle receptors for a wide variety of mono- and oligosaccharides. The boroxole functional monomer bound the sugar templates through cis-1,2-diol, cis-3,4-diol, and trans-4,6-diol. The protein-sized nanoparticles showed excellent selectivity for d-aldohexoses in water with submillimolar binding affinities and completely distinguished the three biologically important hexoses (glucose, mannose, and galactose). Glycosides with nonpolar aglycon showed stronger binding due to enhanced hydrophobic interactions. Oligosaccharides were distinguished on the basis of their monosaccharide building blocks, glycosidic linkages, chain length, as well as additional functional groups that could interact with the nanoparticles.

Selective Recognition of d-Aldohexoses in Water by Boronic Acid-Functionalized, Molecularly Imprinted Cross-Linked Micelles.

Molecular imprinting within cross-linked micelles using 4-vinylphenylboronate derivatives of carbohydrates provided water-soluble nanoparticle receptors selective for the carbohydrate templates. Complete differentiation of d-aldohexoses could be achieved by these receptors if a single inversion of hydroxyl occurred at C2 or C4 of the sugar or if two or more inversions took place. Glycosides with a hydrophobic aglycan displayed stronger binding due to increased hydrophobic interactions.

Enhancing binding affinity and selectivity through preorganization and cooperative enhancement of the receptor.

When direct host-guest binding interactions are weakened by unfavorable solvent competition, guest-triggered intrareceptor interactions could be used to augment the binding. This strategy of cooperative enhancement, when combined with the principle of preorganization, yielded a strong and selective receptor for binding citrate in water.

Conformationally switchable water-soluble fluorescent bischolate foldamers as membrane-curvature sensors.

Membrane curvature is an important parameter in biological processes such as cellular movement, division, and vesicle fusion and budding. Traditionally, only proteins and protein-derived peptides have been used as sensors for membrane curvature. Three water-soluble bischolate foldamers were synthesized, all labeled with an environmentally sensitive fluorophore to report their binding with lipid membranes. The orientation and ionic nature of the fluorescent label were found to be particularly important in their performance as membrane-curvature sensors. The bischolate with an NBD group in the hydrophilic α-face of the cholate outperformed the other two analogues as a membrane-curvature sensor and responded additionally to the lipid composition including the amounts of cholesterol and anionic lipids in the membranes.

Rationally designed cooperatively enhanced receptors to magnify host-guest binding in water.

When disengaged interactions within a receptor are turned on by its guest, these intrahost interactions will contribute to the overall binding energy. Although such receptors are common in biology, their synthetic mimics are rare and difficult to design. By engineering conflictory requirements between intrareceptor electrostatic and hydrophobic interactions, we enabled complementary guests to eliminate the "electrostatic frustration" within the host and turn on the intrahost interactions. The result was a binding constant of Ka >10(5) M(-1) from ammonium-carboxylate salt bridges that typically function poorly in water. These cooperatively enhanced receptors displayed excellent selectivity in binding, despite a large degree of conformational flexibility in the structure.