Purine 5’-Ribonucleotide-l-Glutamate Hybrids As Potential Tools To Investigate The Mechanism Of Umami Taste Reception

Umami taste is elicited predominantly by monosodium glutamate (MSG) and purine 5’-ribonucleotides, in particular guanosine and inosine 5’-monophosphates (GMP and IMP). A significant peculiarity of umami compounds is their capacity to interact synergistically. A possible explanation of such phenomenon is that both L-glutamate and ribonucleotides may interact simultaneously with the “Venus flytrap” domain of T1R1/T1R3 umami receptor, but at different sites. Starting from this model, we reasoned that hybrid compounds, containing the two umami moieties covalently connected through flexible linkers of variable length, could be able to reach both umami receptor sites through a single molecule, thus giving an insight into the mechanism of synergism. MD simulations suggested that a chain of at least eight carbon atoms is requested to allow the interaction of both L-glutamate and 5’-ribonucleotide with their respective binding sites. We report here the synthesis of such hybrids starting from 2’,3’-O-isopropylidene-5’-O-t-butyldimethylsilylguanosine.