Cucurbiturils as Inhibitors of Complex Formation between LL‐37 and DNA

In autoimmune diseases such as psoriasis and lupus, the ability of the LL‐37 peptide to form complexes with DNA plays a significant role in disease onset and pathogenesis. Cucurbiturils have the potential to bind to LL‐37 and to disrupt LL‐37/DNA complexes or to serve as sensors of LL‐37, which may be useful in the treatment of these diseases. Cucurbiturils are macrocyclic molecules that have the ability to form host‐guest complexes with a variety of guest molecules, such as amino acids, drugs, and organic compounds. They bind particularly well to guest molecules that contain cationic, aromatic, and hydrophobic regions, and binding of phenylalanine residues inside the glycouril ring have been observed. At physiological pH, LL‐37 has a net positive charge of +6 and four aromatic phenylalanine residues that may allow LL‐37 to form complexes with cucurbiturils. Electrophoretic mobility shift assays (EMSA) and western blotting were used to study the effect of cucurbit[7]uril on the binding affinity of LL‐37 for 24‐bp DNA fragments with CpG sequences and on LL‐37 self‐association.