Conformational analysis of potent sweet taste ligands by NMR and computer simulations

✍ Scribed by Ralph-Heiko Mattern; Yusuke Amino; Ettore Benedetti; Murray Goodman

• Publisher: Wiley (John Wiley & Sons)
• Year: 1999
• Tongue: English
• Weight: 236 KB
• Volume: 49
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/(sici)1097-0282(199905)49:6<525::aid-bip10>3.0.co;2-3

✦ Synopsis

We report the conformational analysis by 1 H-nmr and computer simulations of five potent sweet molecules, N-(3,3-dimethylbutyl)-L-aspartyl-S-(␣-methyl)phenylalanine methylester (1; 5000 times more potent than sucrose), L-aspartyl-D-valine (S)-␣-methoxycarbonylmethylbenzylamide (2; 1400 times more potent than sucrose), L-aspartyl-D-valine ␣-phenylcyclopentylamide (3; 1200 times more potent than sucrose), L-aspartyl-D-␣-aminobutyric acid (S)-␣-cyclohexylpropylamide (4; 2300 times more potent than sucrose), and L-aspartyl-D-valine (R)-␣-methylthiomethylbenzylamide (5; 3000 times more potent than sucrose). The "L-shaped" structure, which we believe to be responsible for sweet taste, is accessible to all five sweet compounds in solution. This structure is characterized by a zwitterionic ring formed by the A-H and B containing moieties located in the ϩy axis and by the hydrophobic group X pointing into the ϩx axis. Other accessible conformations of these flexible molecules are extended conformations with the A-H and B containing moieties in the ϩy axis and the hydrophobic group X pointing in the -y axis and reversed L-shaped structures with the hydrophobic group X projecting along the Ϫx axis. The remarkable potency of the N-alkylated compound 1 supports our recent hypothesis that a second hydrophobic binding domain in addition to interactions arising from the L-shaped structure leads to an enhancement of sweetness potency.