Modular incorporation of 1-benzyltryptophan into dipeptide hosts that bind acetylcholine in pure water

Proteins that recognize and bind quaternary ammonium ions depend on "aromatic-cage'' structural motifs that use multiple aromatic residues to engage the side chain's ammonium cation. We introduce herein the use of 1-benzyltryptophan (Trp(Bn)) residues as synthetic, unnatural partial analogues of natural aromatic cages. We demonstrate the modular incorporation of these building blocks into simple dipeptide hosts and show that they are capable of binding quaternary ammonium ions in buffered water and in chloroform.