Solid-phase Synthesis and Structure–Taste Relationships of Analogs of the Sweet Protein Monellin

The amino acid residues within potential active sites of monellin were replaced. The replacement of IleB6, AspB7, or IleB8 by different amino acids resulted in a complete or marked loss of sweetness, while the replacement of TyrA13 or AspA16 by other amino acids did not substantially reduce the sweetness. The replacement of each Lys residue by l-2-aminohexanoic acid significantly reduced the sweetness potency, but did not completely remove the sweetness. An analysis of synthetic analogs by CD showed that the major structural features of monellin were not significantly altered. These findings suggest that IleB6, AspB7, and IleB8 are responsible for eliciting a sweet taste, and that one or more basic residues may also be important for sweetness.