Konformationsvoraussetzungen für den süßen Geschmack von Dipeptiden und Dipeptidmimetica

Yamazaki, Toshimasa; Benedetti, Ettore; Kent, Darin R.; Goodman, Murray

doi:10.1002/ange.19941061405

Cited by 7 publications

References 42 publications

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Conformation Analysis of Aspartame‐Based Sweeteners by NMR Spectroscopy, Molecular Dynamics Simulations, and X‐ray Diffraction Studies

et al. 2006

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We report here the synthesis and the conformation analysis by 1H NMR spectroscopy and computer simulations of six potent sweet molecules, N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-S-tert-butyl-L-cysteine 1-methylester (1; 70 000 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-beta-cyclohexyl-L-alanine 1-methylester (2; 50 000 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-4-cyan-L-phenylalanine 1-methylester (3; 2 000 times more potent than sucrose), N-[3,3-dimethylbutyl]-alpha-L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (4; 5500 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-alpha-L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (5; 15 000 times more potent than sucrose), and N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (6; 15 000 times more potent than sucrose). The "L-shaped" structure, which we believe to be responsible for sweet taste, is accessible to all six molecules in solution. This structure is characterized by a zwitterionic ring formed by the AH- and B-containing moieties located along the +y axis and by the hydrophobic group X pointing into the +x axis. Extended conformations with the AH- and B-containing moieties along the +y axis and the hydrophobic group X pointing into the -y axis were observed for all six sweeteners. For compound 5, the crystal-state conformation was also determined by an X-ray diffraction study. The result indicates that compound 5 adopts an L-shaped structure even in the crystalline state. The extraordinary potency of the N-arylalkylated or N-alkylated compounds 1-6, as compared with that of the unsubstituted aspartame-based sweet taste ligands, can be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the L-shaped structure. In our examination of the unexplored D zone of the Tinti-Nofre model, we discovered a sweet-potency-enhancing effect of arylalkyl substitution on dipeptide ligands, which reveals the importance of hydrophobic (aromatic)-hydrophobic (aromatic) interactions in maintaining high potency.

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Conformation Analysis of Aspartame‐Based Sweeteners by NMR Spectroscopy, Molecular Dynamics Simulations, and X‐ray Diffraction Studies

et al. 2006

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Sweet Structural Signatures Unveiled in Ketohexoses

Bermúdez

Peña

Mata

et al. 2016

Chemistry A European J

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The conformational behaviour of naturally occurring ketohexoses has been revealed in a supersonic expansion by Fourier transform microwave spectroscopy coupled with a laser ablation source. Three, two and one conformers of d‐tagatose, d‐psicose and l‐sorbose, respectively, have been identified by their rotational constants extracted from the analysis of the spectra. Singular structural signatures involving the hydroxyl groups OH(1) and OH(2) have been disentangled from the intricate intramolecular hydrogen bond networks stabilising the most abundant conformers. The present results place the old Shallenberger and Kier sweetness theories on a firmer footing.

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ChemInform Abstract: Conformational Requirements for Sweet‐Tasting Peptides and Peptidomimetics

et al. 1994

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Konformationsvoraussetzungen für den süßen Geschmack von Dipeptiden und Dipeptidmimetica

Cited by 7 publications

References 42 publications

Conformation Analysis of Aspartame‐Based Sweeteners by NMR Spectroscopy, Molecular Dynamics Simulations, and X‐ray Diffraction Studies

Conformation Analysis of Aspartame‐Based Sweeteners by NMR Spectroscopy, Molecular Dynamics Simulations, and X‐ray Diffraction Studies

Sweet Structural Signatures Unveiled in Ketohexoses

ChemInform Abstract: Conformational Requirements for Sweet‐Tasting Peptides and Peptidomimetics

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