Pure and Applied Chemistry

Abstract: Structure­taste relationship studies were carried out by chemically synthesizing monellin and its analogs. Replacement of the Asp^B7 by l-2-aminobutyric acid, Gly and d-Asp resulted in complete loss of sweetness. Replacement of Ile^B6 and Ile^B8 by different amino acids resulted in a significant decrease of sweetness, or complete loss of sweetness. Comparison of short- and long-range nuclear Overhauser effects (NOEs) and chemical shifts between monellin and [Abu^B7]monellin showed no marked differences except for the region of the Asp^B7. Thus, the complete loss of sweetness in [Abu^B7]monellin is caused by the lack of free β-carboxyl group in the Asp^B7 and not by a result of major disruption in the overall 3-dimensional structure. These results suggested that the free β-carboxyl group of the Asp^B7 would possibly bind to the receptor site through ionic bonding and trigger the sensation of intense sweet taste, and Ile^B6 and/or Ile^B8 would be involved in the hydrophobic interaction with the receptor site. Selectively labeled monellin was synthesized by the solid-phase method by incorporating ¹⁵N-labeled amino acids into 10 key residues including Asp^B7. Relaxation analysis shows that Asp^B7 is the most flexible of these 10 residues. The flexibility of the active site may be important for receptor binding.