Unravelling the interaction between α-cyclodextrin with the thaumatin protein and a peptide mimic

AbstractG-protein-coupled receptors (GPCRs) are responsible for signal transduction; through these transmembrane proteins, our senses are evoked: sight, smell and taste. Thaumatin is a natural sweet-tasting protein that is 100,000 times sweeter than sucrose but its use in food products has been hampered due to a liquorice aftertaste. Thaumatin has been shown to bind to a class C GPCR and the active binding site of the thaumatin protein is known. Here, we report on the binding of a well-known food grade host: α-cyclodextrin to thaumatin. We show through a combination of one- and two-dimensional NMR experiments that α-cyclodextrin binds to aromatic residues on thaumatin with Ka = 8.5 ± 2.4 M − 1. We also synthesise a heptapeptide KTGDRGF that mimics the active binding site of thaumatin and show that α-cyclodextrin binds to the C-terminal solvent accessible phenylalanine residue of this peptide with Ka = 8.8 ± 3.1 M − 1. This indicates that α-cyclodextrin may interact with the active binding site on thaumatin, suggesting that α-cyclodextrin could be used to modify the interaction of thaumatin with GPCRs and hence its sweet-taste profile.Keywords:: taste modificationG-protein-coupled receptorscyclodextrinpeptide binding studiessupramolecular food chemistry AcknowledgementsThe authors thank the Mark Wainwright Analytical Centre (UNSW) for access to instruments. The authors acknowledge the Australian Research Council for Discovery Project Grant (DP130101512) and a Future Fellowship to PT (FT120100101), support from the Neptune Bio-Innovations to PT and RDH and the Australian Government for PhD scholarship to RDH. VR has equity in Neptune Bio-Innovations Pty. Ltd that supported this work.