The Cucurbit[n]uril Family

Abstract

In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed "cucurbituril" by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants--the pumpkin. In the intervening years, the fundamental binding properties of CB[6]-high affinity, highly selective, and constrictive binding interactions--have been delineated by the pioneering work of the research groups of Mock, Kim, and Buschmann, and has led to their applications in waste-water remediation, as artificial enzymes, and as molecular switches. More recently, the cucurbit[n]uril family has grown to include homologues (CB[5]-CB[10]), derivatives, congeners, and analogues whose sizes span and exceed the range available with the alpha-, beta-, and gamma-cyclodextrins. Their shapes, solubility, and chemical functionality may now be tailored by synthetic chemistry to play a central role in molecular recognition, self-assembly, and nanotechnology. This Review focuses on the synthesis, recognition properties, and applications of these unique macrocycles.

Determining Protease Substrate Selectivity and Inhibition by Label-Free Supramolecular Tandem Enzyme Assays

“…[22][23][24][25] The repeating glycoluril units produce a barrel-shaped container that has a hydrophobic cavity and negatively charged portals. 37 The latter are capable, not only for CB7 but also for its homologues, of binding inorganic cations as well as the cationic sites of organic guests, mostly ammonium groups; nonpolar groups are preferentially immersed in the inner cavity. [38][39][40][41][42] CB7 and its larger homologue CB8 have been shown to bind aromatic amino acids and sequence-specifically to peptides and proteins containing phenylalanine (Phe), tryptophan (Trp), or tyrosine (Tyr) at the N-terminal positions.…”

Molecular switch based on a cucurbit[6]uril containing bistable [3]rotaxane

“…Cucurbituril is prepared from the acid condensation of glycoluril and formaldehyde; it has a hydrophobic cavity, along with two matching hydrophilic carbonyl portals. [6][7][8] Owing to these structural features, CB6 binds well with protonated mono-and di-aminoalkanes mainly through ion-dipole interactions and the hydrophobic effect. Moreover, CB6 has been shown to catalyze 1,3-dipolar cycloaddition between properly functionalized alkyne and azide groups to yield 1,4-disubstituted triazoles.…”

Sequence-Specific Inhibition of a Nonspecific Protease

“…A non-specific exopeptidase, aminopeptidase N (APN), is inhibited sequence specifically by a synthetic host, cucurbit [7]uril (Q7), which binds with high affinity and specificity to Nterminal phenylalanine (Phe) or 4-aminomethyl phenylalanine (AMPhe) and prevents their removal from the peptide. Liquid chromatography experiments demonstrate that in the presence of excess Q7, APN quantitatively converts the pentapeptides Thr-Gly-Ala-X-Met into the dipeptides X-Met (X = Phe or AMPhe).…”

“…4,5 Developing methods that change the substrate specificity of proteases would broaden the scope of their applications. Here we show that a synthetic receptor, cucurbit [7]uril (Q7), can be used to impart specificity to an otherwise non-specific exopeptidase, porcine aminopeptidase N (APN), by binding to a specific residue and inhibiting its removal from the peptide.…”

“…[6][7][8] We and others have studied the capacity of Q7 to bind to amino acids, peptides, and proteins and found that Q7 prefers to bind Nterminal phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp) residues, by incorporating the sidechain within the nonpolar Q7 cavity and chelating the N-terminal ammonium group with Q7 carbonyl oxygens. [9][10][11][12][13][14] Nau and coworkers have shown that Q7 can slow the activity of an endopeptidase, trypsin, and an exopeptidase, leucine aminopeptidase (LAP), by binding to their respective substrates.…”