Solid-phase synthesis of [AsnA16]-, [AsnA22]-, [GlnA25]-, and [AsnA26]monellin, analogues of the sweet protein monellin.
In an attempt to delineate the binding site(s) of monellin to the receptor by means of a structure-taste relationship, we synthesized four monellin analogues, [AsnA16]-, [AsnA22]-, [GlnA25]-, and [AsnA26]-monellin, which were 7500, 750, 2500, and 5500 times as sweet as sucrose on a weight basis, respectively. Among them, [AsnA22]monellin and [GlnA25]monellin were less sweet than monellin, and were susceptible to the HPLC conditions used. It can be concluded that Asp16, Asp22, Glu25, and Asp26 residues of the A chain did not participate in binding with the receptor, since the sweet taste was not removed by replacing the amino acid residues with Asn or Gln. It can also be concluded that Asp22 and Glu25 of the A chain may have participated in intramolecular binding, as was pointed out by Kim et al., since exchanging Asp22 and Glu25 of the A chain with Asn and Gln significantly decreased the stability in solution.
Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
M
M
Kohmura
N
N
Nio
Y
Y
Ariyoshi
D000595:Amino Acid Sequence; D002628:Chemoreceptor Cells / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000138:chemical synthesis*; D013649:Taste / Q000187:drug effects
D010940:Plant Proteins; C002541:monellin protein, Dioscoreophyllum cumminsii