Dipeptide tasting

Aspartame, sweetness production, 28-30 Aspartic acid, as food material, 138-147 Aspartic acid dipeptides, taste, 141-142r Astringpncy, sensation based on generalized membrane responses, 16-18 Automated data analysis and pattern recognition tool kit, 102... 

Goodman, M., Zhu, Q., Kent, D.R., Amino, Y., lacovino, R., Benedetti, E., and Santini, A. (1997). Conformational analysis of the dipeptide taste ligand L-aspartyl-D-2-aminobuty-ric acid-(S)-alpha-ethylbenzylamide and its analogues by NMR spectroscopy, computer simulations and X-ray diffraction studies. J. Pept. Sci. 3,231-241. 

The binding specificity of d-[ C]glucose by the taste-papillae membranes, compared to that of control membranes isolated from epithelial tissue, has been confirmed in two studies. One inherent problem in the approach is that the stimuli, primarily carbohydrate sweeteners, are not ideal model compounds to use, as they are not active at low concentrations and do not show sufficiently high binding-constants. The use of other stimulus compounds that are at least several hundred times sweeter than sucrose, such as saccharin, dihydrochalcone sweeteners, dipeptide sweeteners, stevioside, perillartine and other sweet oximes, the 2-substituted 5-nitroanilines, and... 

Cyclo(Leu-Trp), a bitter compound isolated from the fermentation of milk casein by Bacillus subtilis, opened up the field to flavor and fragrance properties. It was further noted that dipeptides became more bitter when blockage of both the amino and carboxyl groups occurred or the dipeptide was converted into a DKP. This phenomenon opened the field of taste exhibition. ... 

During work on a series of aspartyl dipeptides containing ACC 71 (vide supra, Eq. (28), Sect. 4) at the carboxyl terminus, it was reported that dispartame Asp-ACC-OMe had a distinct sweet taste [302] and that the corresponding n-propyl ester had 250-300 times the sweetness of sucrose [303]. However, replacement of phenylalanine by 2,3-methanophenylalanine gave tasteless analogues of aspartame [293, 304], and some dimethyl-ACC 214 (methanovaline) and tri-methyl-ACC 215 aspartame analogues [Asp-(Me)n-ACC-OMe] have a bitter taste. These taste properties, which depend on the number and position of the methyl substituents, have been explained on the basis of topochemical models thus, a L-shaped conformation of the dipeptide is necessary for sweet taste, Eq. (86) [3051. 

Many bixxer compounds contain both hydrophobic and hydrophilic sites which can alter cell membranes through penetration. There is a correlation between bitter intensity and hydrophobicity-solubility indexes such as fee octanol/water partition coefficient, lo (7). Penetration may directly affect cAMP phosphodiesterase as part of fee transduction process (see below). A bitter receptor protein may be involved wife certain bitters, such as specific structural requirements wife fee bitter tasting dipeptides and denatonium salts (27). The latter is used in some consumer products to avoid accidental ingestion. A receptor mechanism is also supported by fee existence of a genetic "taste blindness" for some bitter materials (see below). 

Bitter taste can be masked by sweeteners, by salt or by dipeptides containing aspartic or glutamic acids (22,25,24,25). The bitter-masking potential of sugars wife quinine was recently assessed, and quinine-equivalent values were derived to predict masking ability of these substances. Attenq)ts to mask bitter taste may be successful only wife certain bitter substances. 

The role of aspartic acid and glutamic acid was investigated in BMP (Beefy Meaty peptide, Lys-Gly-Asp-Glu-Glu-Ser-Leu-Ala) isolated from enzymatic digests of beef soup. The taste of BMP was affected by the sequence of acidic fragment. Sodium ion uptake of acidic dipeptides and their taste, when mixed with sodium ion, were dependent on the component and/or sequence of dipeptides containing acicHc amino acids. 

Sensory analysis of mixed solutions of MSG and each of four dipeptides was carried out (Table VI). The umami taste of MSG was not changed when it was mixed with peptides containing aspartic acid. On the other hand, Glu-Glu, produced the... 

Taste Score of Mixed Solutions of MSG and Acidic Dipeptides... 

Taste of Dipeptides Containing Lys and/or Gly. Since Lys-Gly HCl produces the saltiness, we prepared some dipeptides composed of Lys and/or Gly. The results are listed in Table XI. Gly-Lys, of which the amino acid sequence is opposite to the salty peptide Lys-Gly-HCl, produced a weakly sweet taste instead of the salty taste. Dipeptide composed of only Lys or Gly did not any taste. 

Re-formation of the Taste of BMP. According to the above results, the taste of BMP might produced by the combination of the basic amino acid (Lys) at N-terminal and acidic amino acids at the middle part. To confrnn this idea, we prepared a mixed solution of the N-terminal dipeptide (Lys-Gly), the acidic tripeptide at the middle part (Asp-Glu-Glu) and C-terminal tripeptide (Ser-Leu-Ala) and examined the taste. We also studied tastes of a mixture in which a basic dipeptide fragment was replaced by Orn-p-Ala, a salty dipeptide, and a mixture in which Glu-Glu replaced an acidic tripeptide fragment. The result are shown in Table XIV. All of the combinations produced the same character of the taste as BMP. It means that the taste of BMP is mainly produced by the combined effect of the N-terminus basic dipeptide and the acidic tripeptide of the middle part. However, taste strength of the mixture became... 

Salty taste enhancing preparations or compounds besides KCl were described. For example, a mixture of certain amino acids based on L-lysine were used to increase the saltiness of a NaCl-reduced preparation [34] y-aminobutyric acid (4) was also used as a salty taste enhancer [35]. Some dipeptides such as N-l-ornithyl taurine hydrochloride or N-L-lysinyl taurine hydrochloride were described as very salty with a clean salt taste [36]. Additionally, choline chloride was suggested as a salt enhancer [37]. 

The analysis, in composite over the four classes of L-aspartyl dipeptides suggests that the electron-withdrawing effect of substituents directed to the peptide bond, and the steric dimensions of the molecules, are important in eliciting the sweet taste. The values of the regression coefficients of the a term in the QSAR equations for L-aspartic acid amides, L-aspartylaminoethylesters, and L-aspartylaminopropionates all... 

Aspartame. Aspartame [22839-47-0] [53906-69-1] (APM, L-aspartyl-L-phenylalanine methyl ester) (1), also known under the trade names of NutraSweet and EQUAL, is the most widely used nonnutritive sweetener worldwide. This dipeptide ester was synthesized as an intermediate for an antiulcer peptide at G. D. Searle in 1965. Although this compound was known in the literature, its sweet taste was serendipitously discovered when a chemist licked his finger which was contaminated with it. Many analogues, especially the more stable esters, were made (6) and their taste qualities and potencies determined. It was the first compound to be chosen for commercial development. Following the purchase of G. D. Searle by Monsanto, the aspartame business was split off to become a separate Monsanto subsidiary called the NutraSweet Company. 

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-... 

R. H. Mazur, J. M. Schlatter, and A. H. Goldkamp, Structure-taste relationships of some dipeptides,... 

The sweet dipeptide esters of the L-aspartic acid and the L-amino malonic acid (15-21) are interesting exceptions to the bitter taste shared by all other members of the peptide series. Fig. 

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. 

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... 

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. 

The studies on peptides began with a correlation between sweet amino acids and peptides. Since the projection formula of L-Asp-Gly-OMe (4) is similar in size and shape to that of e-Ac-D-Lys (3) which is sweet, we predicted that L-Asp-Gly-OMe would taste sweet in spite of the bitter taste in the literature. Therefore, we synthesized the peptide and tasted it. As expected, it was sweet and its sweetness potency was almost equal to that of e-Ac-D-Lys. Thus, the dipeptide could be correlated to the amino acid. Lengthening (5) or enlargement (6) of the alkyl group of the ester did not affect its sweetness potency (Table 1). 

Therefore, we have concluded that sweet-tasting aspartyl dipeptide esters can be drawn as the unified formula (A), whereas nonsweet peptides as (B) as shown in Figure 1. 

In Ama-L-Phe-OMe (47) (14, 15), it is also not known whether the sweet-tasting isomer has the L-L(or S-S) or the D-L(or R-S) configuration. In the case of aspartyl dipeptide esters, the L-L isomer was sweet. By analogy, other researchers deduced that the L-L(or S-S) isomer ((47b) in Figure 4) would be sweet. However, it seemed to us that the D(or i )-configuration would be preferred for the aminomalonic acid because the D-L(or R-S) isomer ((47a) in Figure 4) was compatible with the sweet formula and could also fit the spatial barrier model (13), whereas the L-L(or S-S) isomer could neither fit the receptor model nor meet the sweet formula. 

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. 

Finally, L-Asp-D-Val-Gly-OMe (41) was synthesized in order to see whether it remained sweet. The peptide was devoid of sweetness and almost tasteless, though D-valine-containing aspartyl dipeptide esters such as L-Asp-D-Val-0Pr (17) and L-Asp-D-Val-OPrt (8, 17), which are similar to the tripeptide ester in size and shape and have potent sweet taste. 

The f values of the single amino acids given in Table I were determined by Tanford (2) from solubility data and they represent a measure of the hydrophobicity of an amino acid residue. Please note, that the values are relative to the methyl groups of glycine which is taken to be O. In Table II the taste of some "isomericn-dipeptides is described. All the dipeptides are composed of the natural 1-amino acids, as are all the examples, that will follow later. It is interesting to note, that the position of the amino acid has no influence on bitterness ( ). 

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