The supramolecular chemistry of natural sweeteners

The sense of taste is as ubiquitous and essential to us as the other senses of touch, sight, hearing and olfaction. The simple process of tasting a food involves an intricate and complex series of microscopic biological events, the first step of which involves supramolecular molecular recognition between taste receptors and tastant molecules. Complex taste profiles of foods, such as the lingering sweetness of natural sweeteners, remain poorly defined biophysical phenomena. Furthermore, elucidating mechanisms involved with lingering sweet taste allows insight into other receptor mediated lingering effects. G protein-coupled receptors (GPCRs) allow transmission of local and long distance signalling within the body. They are intrinsic to almost every pathway involving cell-cell communication and extracellular recognition of stimuli including taste, olfaction and sight. Over 800 GPCRs have been identified in the human genome and over 40 50% of drugs currently on the market target this diverse range of integral membrane proteins. The sweet-taste receptor is a family C GPCR, characterized by a natively dimeric state and a large extracellular domain. Through this receptor, all sweet taste is transduced in the oral cavity, however this receptor is also found in pancreatic, intestinal and brain tissue. What the function of sweet-taste receptors is in tissue outside the oral cavity and how natural and artificial sweeteners activate them is currently under scrutiny. The most potent sweetener on earth is a naturally occurring 22 kilodalton protein – thaumatin. The widespread industrial use of thaumatin as a low calorie alternative is hampered by its taste profile, exhibiting some bitter notes and a lingering sweet taste. The molecular mechanisms underlying thaumatins’ unique temporal taste profile remain unclear. Chapter 2 of this thesis explores the potential use of supramolecular host:guest chemistry to modify the sweet taste profile of thaumatin. Alpha-cyclodextrin has been investigated as a supramolecular complexing ...