Conformation analysis of aspartame-based sweeteners by NMR spectroscopy, molecular dynamics simulations, and X-ray diffraction studies. (Articolo in rivista)

Type
Label
  • Conformation analysis of aspartame-based sweeteners by NMR spectroscopy, molecular dynamics simulations, and X-ray diffraction studies. (Articolo in rivista) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1002/cbic.200500332 (literal)
Alternative label
  • De Capua, Antonia; Goodman, Murray; Amino, Yusuke; Saviano, Michele; Benedetti, Ettore (2006)
    Conformation analysis of aspartame-based sweeteners by NMR spectroscopy, molecular dynamics simulations, and X-ray diffraction studies.
    in ChemBioChem (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • De Capua, Antonia; Goodman, Murray; Amino, Yusuke; Saviano, Michele; Benedetti, Ettore (literal)
Pagina inizio
  • 377 (literal)
Pagina fine
  • 387 (literal)
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  • 7 (literal)
Rivista
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  • Pubblicazione su rivista scientifica (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • Univ Naples Federico 2, CNR, Dept Biol Sci, Inst Biostruct & Bioimaging, I-80134 Naples, Italy CIRPeB, I-80134 Naples, Italy Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA Ajinomoto Co Inc, AminoSci Labs, Kawasaki Ku, Kawasaki, Kanagawa 218681, Japan (literal)
Titolo
  • Conformation analysis of aspartame-based sweeteners by NMR spectroscopy, molecular dynamics simulations, and X-ray diffraction studies. (literal)
Abstract
  • We report here the synthesis and the conformation analysis by (1)H 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; 70000 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-beta-cyclohexyl-L-alanine 1-methylester (2; 50000 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-beta-cyan-L-phenyloalanine 1-methylester (3; 2000 times more potent than sucrose), N-[3,3-dimethylbutyl]-alpha-L-aspartyl-(1R,2S,4S)-7-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; 15000 times more potent than sucrose), and N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-asaortyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (6; 15000 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. (literal)
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