Targeted Polypeptide-Microtubule Aggregation with Cucurbit[8]uril for Enhanced Cell Apoptosis

Area of Science:

• Supramolecular Chemistry
• Biochemistry
• Materials Science

Background:

• Tunable protein assemblies are crucial in biological processes and supramolecular chemistry.
• Microtubules (MTs) are key protein structures whose aggregation influences biological events.

Purpose of the Study:

• To demonstrate the regulation of microtubule intertubular aggregation using synergistic polypeptide-tubulin interactions and host-guest complexation.
• To explore the therapeutic potential of targeted ternary assemblies for cancer treatment.

Main Methods:

• Utilized a benzylimidazolium-modified antimitotic peptide (BP) for microtubule recognition.
• Employed cucurbit[7]uril (CB[7]) and cucurbit[8]uril (CB[8]) for host-guest complexation with the peptide.
• Investigated the self-assembling morphology changes of MTs induced by BP⊂CB[8] cross-linkage.

Main Results:

• BP formed stable inclusion complexes with CB[7] and CB[8] in varying stoichiometries.
• The BP⊂CB[8] cross-linkage transformed fibrous MT aggregates into nanoparticulate ones.
• Achieved significant in vivo cell apoptosis and tumor ablation through the targeted (BP⊂CB[8])@MT ternary assembly.

Conclusions:

• The targeted (BP⊂CB[8])@MT ternary assembly offers a novel supramolecular strategy to enhance protein-protein interactions.
• This approach holds promise for developing new therapies for degenerative diseases, including cancer.