Human Taste and Umami Receptor Responses to Chemosensorica Generated by Maillard-type N 2‑Alkyl- and N 2‑Arylthiomethylation of Guanosine 5′-Monophosphates

Structural modification of the exocyclic amino function of guanosine 5′-monophosphate (5′-GMP) by Maillard-type reactions with reducing carbohydrates was recently found to increase the umami-enhancing activity of the nucleotide upon S-N 2-1-carboxyalkylation and S-N 2-(1-alkylamino)carbonylalkylation, respectively. Since the presence of sulfur atoms in synthetic N 2-alkylated nucleotides was reported to be beneficial for sensory activity, a versatile Maillard-type modification of 5′-GMP upon reaction with glycine’s Strecker aldehyde formaldehyde and organic thiols was performed in the present study. A series of N 2-(alkylthiomethyl)guanosine and N 2-(arylthiomethyl)guanosine 5′-monophosphates was generated and the compounds were evaluated to what extent they enhance the umami response to monosodium l-glutamate in vivo by a paired-choice comparison test using trained human volunteers and in vitro by means of cell-based umami taste receptor assay. Associated with a high umami-enhancing activity (β-value 5.1), N 2-(propylthiomethyl)guanosine 5′-monophosphate could be generated when 5′-GMP reacted with glucose, glycine, and the onion-derived odorant 1-propanethiol, thus opening a valuable avenue to produce high-potency umami-enhancing chemosensorica from food-derived natural products by kitchen-type chemistry.