Cucurbit[7]uril (CB[7])

Cucurbit[7]uril (CB[7]) is a synthetic macrocyclic molecule composed of seven glycoluril units, forming a rigid, pumpkin-shaped structure with a hydrophobic cavity and two carbonyl-fringed portals (Kim, K., 2002, Chemical Society Reviews). It serves as a non-physiological supramolecular host that exhibits high affinity for cationic and hydrophobic guest molecules, such as the diabetes drug pramlintide (Maity, I., et al., 2016, Chemical Communications). Pramlintide, a synthetic analog of human amylin, is highly prone to aggregation into toxic amyloid fibrils, which limits its clinical utility and prevents its co-formulation with insulin. By encapsulating the N-terminal residues of pramlintide, CB[7] provides steric hindrance that prevents peptide-peptide interactions and subsequent fibrillization, effectively stabilizing the peptide in its active monomeric state (Webber, M. J., et al., 2016, PNAS). This interaction is purely supramolecular and does not involve covalent bonding, allowing the drug to be released upon dilution or competition in the physiological environment. Beyond its application in diabetes, CB[7] is investigated for its ability to reverse the effects of neuromuscular blocking agents and to improve the delivery of various chemotherapeutic agents (Zhang, X., et al., 2019, Chemical Society Reviews).

Other names

CB7CB[7]CucurbiturilMacrocyclic hostGlycoluril oligomer

Supramolecular host-guest encapsulation of the N-terminal residues (specifically the ammonium group and hydrophobic side chains) of pramlintide to provide steric hindrance against amyloid fibril formation and enhance formulation stability.