Sweet-taste inhibitors

Inhibitors. Sugar is used in large quantities in fmit jams as a preservative. The strong sweetness, however, prevents fmity flavors from being noticed. For these and other foods that must use a large amount of sugar for purposes other than sweet taste, there is need for a sweet-taste inhibitor. 

Lactisole [13794-15-5] the sodium salt of racemic 2(4-methoxyphenoxy)propionic acid, is a sweet-taste inhibitor marketed by Domino Sugar. It was affirmed as a GRAS flavor (FEMA no. 3773). At a concentration of 100 to 150 ppm, lactisole strongly reduces or eliminates the sweet taste of a 10% sugar solution. This inhibition appears to be receptor-related because lactisole also inhibits the sweet taste of aspartame. The 5 -( —)-enantiomer [4276-74-8] (38), isolated from roasted coffee beans, is the active isomer the i -(+)-enantiomer is inert (127). 

Mathlouthi, M. Macjejewski, C., Serghat, S., Hooft, R.W., Kanters, J.A., and Kroon, J. Structural studies on sweet taste inhibitors methyl-4,6-dichloro-4,6-dideoxy-galactopyranoside, /. Mol. Struct., 291,173, 1993. 

Mathlouthi M., Angisbout J.F., Kacurakova M., Hooft R.W., Kanters J.A. and Kroon J. (1994) Structural studies on sweet taste inhibitors lactisole, DL-2(4-methoxyphenoxy)-propanoic acid. J. Mol. Struct. 326 (1-3), 25 34 (Chem. Ahstr. 122, 28808). 

Brazzein is another small sweet-tasting protein whose solution structure has been recently solved by NMR. Brazzein tastes 2000 times sweeter than sucrose on a weight basis and is exceptionally thermostable. As indicated by NMR, the structure of this 54 residue, single-chain polypeptide does not change between 32 and 82 °C and retains its sweetness after incubation at 98 °C for two hours.Brazzein contains one a-helix and three strands of antiparallel jd-sheet stabilized by four intramolecular disulphide bonds. It has been proposed that the disulphide bonds could be responsible for the thermostability of brazzein by forming a compact structure at the tertiary level.The structure of brazzein does not resemble that of the other two sweet proteins with known structures, monellin and thaumatin, whereas sequence alignment and structural prediction indicate that brazzein shares the fold of a newly identified family of serine proteinase inhibitors. 

Quinine also has pharmacological activity as an antimalarial, and some studies have been made in order to find a method to diminish or suppress its bitter taste. This can be achieved by adding sweet compounds such as sucrose or aspartame or nonspecific bitter taste inhibitors such as NaCl or phosphatidic add and tannic add [39]. The effects have been studied by sensory evaluation tests in human volunteers, a binding... 

Interestingly, the human TAS1R2/TAS1R3, but not its mouse counterpart, are sensitive to the sweet proteins monellin, thaumatin, and brazzein, and to the artificial sweeteners neo-tame, cyclamate, and aspartame (9-11). This difference provides a molecular explanation for the previous observation that these compounds are sweet for humans but not attractive to rodents (9). The species difference also applies to the inhibitor lactisole that blocks the sweet taste in humans but not in rats, and only inhibits the response of human TAS1R2/TAS1R3 to sweet stimuli (9). 

Besides the naturally occurring saccharides and polyols, there are a number of plant-derived highly sweet compounds, which are mostly terpenoids, flavonoids, and proteins [16-18]. Several of these sweet substances are used commercially as sucrose substitutes, as will be described in the next section. In addition, a number of plant substituents are known to mediate the sweet-taste response, either by inducing or inhibiting the perception of sweemess [19]. Thus far, all of the known natural product sweet-tasting substances and sweetness modifiers have been obtained from green plants [16-19]. In the remaining sections of this chapter, plant-derived sweet compounds with commercial use will be described, followed by a section on recent theories on the sweet taste phenomenon, and then individual descriptions of potent sweeteners, sweetness inducers, and sweetness inhibitors from plants will be presented in turn. The literature has been surveyed for this chapter until the end of 1999. 

Murzin, A.G. (1993). Sweet-tasting protein monellin is related to the cystatin family of thiol proteinase inhibitors. J. Mol. Biol. 230, 689-694. 

It is also well known that sweet and bitter tastes interact. It is the case for the inhibition of sucrose sweet taste by inhibitors like lactisol or methyl-4, 6-dichloro-4,6-dideoxy-galactopyranoside which was attributed to their hydrophobic character and their bitterness (Mathlouthi et al., 1993). Bitter taste was foimd to be suppressed by sweeteners such as sucrose (Bartoshuk, 1975). The masking of unpleasant taste by pleasant (sweet) stimuli is greatly sought after in pharmaceuticals. For example, cyclodextrins were described to have the ability of masking the bitterness of drugs like propantheline... 

Several natural products are known to modify the sense of sweet taste. Such compounds can be either sweetness inhibitors or sweetness inducers/enhancers. A review of Suttisri et al., 1995 summarizes data on phytochemistry and biological activity of more than 40 triterpenoid sweetness inhibitors based on the oleanane and dammarane skeletons. These saponins were isolated from the leaves of Gymnema sylvestre, Zizyphus jujuba and Hovenia dulcis [224]. Recently, antisweet oleanane-type saponins were isolated from Stephanotis lutchuensis vm. japonic a [225]. 

Constit. of latex of Dyera lowii and in the leaves of Anodendron affine. Also from Nerium oleander, Trachelospermum jasminoides and other plants. Latex used for manuf of chewing gum. Allergy inhibitor. Cryst. (EtOH) with sweet taste. Mp 210°. Exhibits polymorphism. Opt. inactive (meso-). 

At least 10 of jujube s saponins (e.g. ziziphin, jujubasaponins, and jujuboside B) are sweetness inhibitors that reduce the sensation of sweet taste (elevate the sweetness threshold) of glucose, fructose, aspartame, and other sweetening agents. No taste modifying effect was observed with bitter, salty, or sour flavors. 

The best-known sweetness inhibitor is sodium dodecyl sulfate (SDS), also known as sodium lauryl sulfate. This substance is a twelve carbon surfactant that is quite commonly used as a detergent in toothpaste. The observation is often made that after brushing one s teeth, the taste of orange juice is unusually bitter. This has been ascribed to the presence of SDS in the dentifrice (6 ). 

This compound has been patented (Tate Lyle PLC) as a flavoring agent. It has only an acid taste but could be used to modify high sweetness. The sodium salt is a selective inhibitor of the sweetness of sucrose and has been used in aqueous solution to elucidate the mechanism of this inhibition (Mathlouthi et al., 1994). 

---