title: Stereoselective synthesis of amides sharing the guanosine 5'-monophosphate scaffold and Umami enhancement studies using human sensory and hT1R1/rT1R3 receptor assays.
abstract: Recent studies led to the identification of umami-enhancing (S)-N(2)-(1-carboxyethyl)- and (S)-N(2)-(1-alkylamino)carbonylalkyl)guanosine 5'-monophosphates that, together with their sensorially inactive (R)-stereoisomers, were found to be formed upon Maillard-type glycation of guanosine 5'-monophosphate (5'-GMP) with 1,3-dihydroxyacetone or glyceraldehyde, respectively. As the efficiency of this Maillard-type procedure to generate the amidated derivatives is limited by the low solubility and reactivity of long-chain alkyl amines as well as by the tedious separation of the diastereomers formed, a versatile synthesis for the (R)- and (S)-configured amides of N(2)-carboxyalkylated guanosine 5'-monophosphate was developed. Sensory evaluation of a series of N(2)-(1-alkylamino)carbonylalkyl)guanosine 5'-monophosphates revealed β-values for umami enhancement between 0.1 and 7.7 and identified a strong influence of the stereochemistry as well as the chain length of the N(2)-substituent on the umami-enhancing activity. The observed sensory impact of the (S)-configured isomers was confirmed by recording the enhancing effect of these nucleotides on the l-glutamate-induced response of the functionally expressed T1R1/T1R3 umami receptor in a cell-based assay, thus underscoring the stereospecifity of the umami taste receptor binding site.
authors.affiliation: Chair of Food Chemistry and Molecular Sensory Science, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Festring
authors.forename: Anne
authors.initials: A
authors.lastname: Brockhoff
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D018698:Glutamic Acid / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000737:chemistry*; D006801:Humans; D015416:Maillard Reaction; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000502:physiology; D012903:Smell; D013237:Stereoisomerism; D013649:Taste
chemical_list: D000577:Amides; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D018698:Glutamic Acid; D006157:Guanosine Monophosphate