Structure sweet peptide

Today, it is well-known that peptides or proteins exhibit various kinds of taste. Our group has been researching on the relationship between taste and structure of peptides, BPIa (Bitter peptide la, Arg-Gly-Pro-Pro-Phe-Ile-Val) (7 as a bitter peptide, Om-p-Ala-HCl (OBA), Om-Tau-HCl as salty peptides(2j, and "Inverted-Aspartame-Type Sweetener" (Ac-Phe-Lys-OH) as a sweet peptide(5). The relationship between taste and chemical structure was partly made clear. Since commercial demand for these flavor peptides is increasing, we need to develop new synthetic methods which can prepare these peptides in large scale. We developed the following two methods (1) protein recombination method as a chemical method, (2) enzymatic synthesis using chemically modified enzyme as a biochemical method. 

After the finding of a sweet taste in L-Asp-L-Phe-OMe (aspartame) by Mazur et at. (6), a number of aspartyl dipeptide esters were synthesized by several groups in order to deduce structure-taste relationships, and to obtain potent sweet peptides. In the case of the peptides, the configuration and the conformation of the molecule are important in connection with the space-filling properties. The preferred conformations of amino acids can be shown by application of the extended Hiickel theory calculation. However, projection of reasonable conformations for di- and tripeptide molecules is not easily accomplished. 

Figure 1. General structure for sweet peptides R, = small hydrophobic side chain (1 4 atoms) R2 = larger hydro-phobic side chain (3 6 atoms) (4)...

The structure-taste relationships will be discussed in detail. Dipeptide esters are closely related to amino acids in chemical structure and properties. Hence, we selected amino acids as the standard to which sweet peptides were related. The structural features of sweet-tasting amino acids have been best explained by Kaneko (12) as shown in Figure 2, in which an amino acid will taste sweet when R2 is H, CH3 or C2H5, whereas the size of Ri is not restricted if the amino acid is soluble in water. 

One problem that remains is the mode of interaction between the sweet peptides and the receptor site. Despite a great number of studies, the mechanism of action of sweet stimuli on the receptor is not well known. Stereoisomerism can be responsible for differences in taste responses, and space-filling properties are also very important. These facts suggest that the receptor site exists in a three-dimensional structure. In this connection, the sense of sweet taste is subject to the "lock and key" of biological activity. 

Yusuke Amino was born injapan in 1958. He received his master degree in 1983 and Ph.D. in 1991 from Kyoto University under the direction of Professor Takeo Saegusa and Professor Yoshihiko Ito. In 1983, he joined the Central Research Laboratories of Ajinomoto Co., Inc. He studied a natural product synthesis at Colorado State University (with Professor R. M. Williams) from 1991 to 1993. After studying the chemistry of sweet peptides at UCSD (with Professor M. Goodman) in 1994, he returned to Ajinomoto Co., Inc. Since then, he has been working on the structure—activity relationships of taste compounds. 

Short oligopeptides play an important role in the sensorial appreciation of food and much attention has been paid to the relationship between the structure of peptides and their taste, based on four basic taste sensations (sweet, bitter, sour and salty). 

Sweetness is a quality that defies definition, but whose complexity can be appreciated merely by examining the molecular structures of those compounds that elicit the sensation. They come in all molecular shapes and sizes, and they belong to such seemingly unrelated classes of compounds as aliphatic and aromatic organic compounds, amino acids, peptides and proteins, carbohydrates, complex glycosides, and even certain inorganic salts. 

Gum acacia is a unique polysaccharide, with some peptides as part of the structure and has a range of different uses. It was originally the gum in gum sweets although some gum sweets do contain modified starch as a substitute. The replacement of gum is not because the substitute performs better but because there have been supply problems with gum acacia. Gum acacia is likely to be encountered in bakeries in small quantities when it has been used to make emulsions of citrus oils as a bakery flavour. It is possible to use gum acacia in making dry flavours from oils such as citrus by making an emulsion and then spray drying it. 

Sweetness Production by the Combination of Bitter and Sweet Tastes. Sensory tests using typically bitter compounds such as brucine, strychnine, phenylfiiiourea, caffeine and bitter peptides were performed. Sensory tests using typically bitter compounds such as brucine, strychnine, phenylthiourea, caffeine and bitter peptides were performed. Sensory taste impression were also measured for combinations of acetic acid (sour) and typical bitter compounds (5). The data from these studies indicated that the tastes of ese bitter/sour mixtures changed to a sweet taste regardless of their chemical structure of the bitter component (Table II). 

Other peptides, such as L-aspartyl-L-phenylalanine methyl ester (aspartame), have a sweet taste. Several studies have been carried out to relate the structure and taste of analogs of this dipeptide (25). Tsang et al. (26) reported that the analogs at the lower end of the L-aspartyl-a-aminocycloalkanecarboxylic acid methyl ester series were sweet, the dipeptides containing a-... 

In the course of investigations of aspartyl dipeptide esters, we had to draw their chemical structures in a unified formula. In an attempt to find a convenient method for predicting the sweettasting property of new peptides and, in particular, to elucidate more definite structure-taste relationships for aspartyl dipeptide esters, we previously applied the Fischer projection technique in drawing sweet molecules in a unified formula 04). 

The sweet-tasting property of aspartyl dipeptide esters has been successfully explained on the basis of the general structures shown in Figure 1 (4). A peptide will taste sweet when it takes... 

B). This also suggests that the AH-B concept represents only a first approximation in the case of peptides. Certainly, the AH-B system is required in the molecule. However, the structural characteristics of the second amino acid sometimes may completely mask any AH-B effect. To test the above hypothesis, we have synthesized a number of peptides with or without a sweet taste. 

Further examinations of the molecular features and of the model of receptor have suggested that several aspartyl tripeptide esters may also taste sweet. In confirmation of the idea, several tripeptide esters have been synthesized. In the first place, L-Asp-Gly-Gly-OMe (38) was synthesized as an arbitrarily-selected standard of tripeptides, because it was considered that this peptide ester had the simplest structure, and correlation of other peptides to (38) was easy. The tripeptide ester was predicted that it would be slightly sweet or tasteless because its projection formula was similar in size and shape to that of L-Asp-Gly-0Bum which is 13 times sweeter than sucrose (16) and because it is more hydrophilic than the dipeptide. The tripeptide (38) was devoid of sweetness and almost tasteless. 

The simplest tastant, the hydrogen ion, is perceived as sour. Other simple ions, particularly sodium ion, are perceived as salty. The taste called umami is evoked by the amino acid glutamate, often encountered as the flavor enhancer monosodium glutamate (MSG). In contrast, tastants perceived as bitter or sweet are extremely diverse. Many bitter compounds are alkaloids or other plant products of which many are toxic. However, they do not have any common structural elements or other common properties. Carbohydrates such as glucose and sucrose are perceived as sweet, as are other compounds including some simple peptide derivatives, such as aspartame, and even some proteins. 

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