title: Systematic studies of structure and physiological activity of alapyridaine. A novel food-born taste enhancer.
abstract: By application of taste dilution analysis (+)-(S)-1-(1-carboxyethyl)-5-hydroxy-2-(hydroxymethyl)-pyridinium inner salt was recently successfully identified as a multimodal taste enhancer in beef bouillon. While being taste-less on its own, this so-called alapyridaine was found to intensify the human perception of sweet, salty, and umami taste. To gain information on the molecular requirements of this novel class of taste enhancer, a range of structurally related pyridinium betaines were synthesized, purified, and their physiological activities sensorially evaluated. Removal or modification of the hydroxyl and the hydroxymethyl group, respectively, induced a loss in bioactivity, thus indicating the 2-(hydroxymethyl)-5-hydroxypyridinium moiety as an essential structural element for taste enhancement. Regarding the amino substituent, neither the prolongation or removal of the alkyl chain or the carboxy function in the 1-(1-carboxy-2-ethyl)-moiety, nor the incorporation of an additional carboxy function led to any active derivative, thus demonstrating that also the structure of the nitrogen substituent is rather conserved for taste enhancement. But substitution of the methyl group by a benzyl group yielded a compound showing similar taste enhancing activities as found for alapyridaine. Interestingly, additional insertion of glycine between the 1-(1-carboxy-2-phenylethyl)-moiety and the pyridinium ring resulted in a compound eliciting comparable taste enhancing effects as shown for the compound lacking the glycine spacer. In contrast to these multimodal taste enhancers, substitution of the alanine moiety in alapyridaine by an arginine moiety revealed an one-dimensional taste enhancer exclusively increasing the human sensitivity for salty taste.
authors.affiliation: Deutsche Forschungsanstalt für Lebensmittelchemie, Garching, Germany.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Soldo
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Harald
authors.initials: H
authors.lastname: Ottinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000596:Amino Acids / Q000032:analysis; D002241:Carbohydrates; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005421:Flavoring Agents; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013649:Taste / Q000187:drug effects*
chemical_list: D000596:Amino Acids; D002241:Carbohydrates; D005421:Flavoring Agents; D011725:Pyridines; C472251:alapyridaine; D000409:Alanine