Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein-Ligand Interactions

Artificial tubular molecular pockets bearing polar functionalities on their inner surface are useful model systems for understanding the mechanisms of protein-ligand interactions in living systems. We herein report a pillar[5]arene-derived molecular tube, [P4-(OH)BPO], whose endo conformational isomer endo-[P4-(OH)BPO] possesses an inwardly pointing hydrogen-bond (H-bond) donor (OH) in its deep cavity, a strong H-bond acceptor (C=O) on the predominantly hydrophobic inner surface, rendering it a perfect protein binding pocket mimetic. By measuring the binding affinity of this pocket-mimetic tube, we screened a library of various shape-complementary organic guests (1–38) resembling the fragment ligands in fragment-based drug design (FBDD). On the basis of the data for “fragment-pocket” complexes (1–38)⊂endo-[P4-(OH)BPO], two rationally designed “lead molecules” (39 and 40) were identified to be able to enhance binding affinity significantly by forming H-bonds with both the donor and acceptor of endo-[P4-(OH)BPO]. The described work opens new avenues for developing pillar[n]arene-derived protein binding pocket-mimetic systems for studies on protein-ligand interactions and mechanisms of enzymatic reactions.

A novel molecular tube fully modified at one end: selective inclusion of cis-unsaturated fatty acid esters

A cyclodextrin tube with one fully modified and one unmodified end selectively includes cis-unsaturated fatty acid esters.

Synergistic host–guest hydrophobic and hydrogen bonding interactions in the complexation between endo-functionalized molecular tube and strongly hydrophilic guest molecules in aqueous solution

Molecular dynamics simulation study of the recognition of hydrophilic molecules by an endo-functionalized molecular tube in aqueous solution.

An aqueous molecular tube with polyaromatic frameworks capable of binding fluorescent dyes

An aqueous polyaromatic tube binds two molecules of fluorescent dyes in water and the bound dye dimers exhibit unusual excimer-like emissions through efficient host–guest energy transfer.