Sweeteners model development

FIGURE 4 Three of the most popular indirect models of the active site of the sweet taste receptor. (A) Main contour ofthe active site proposed by Temussi and coworkers (Kamphuis et al., 1992 Temussi et al., 1978,1984,1991), hosting a molecular model of aspartame in an extended conformation. (B) A topological model, developed by Goodman et al. (1987). The L -shaped model and an L -shaped conformation of aspartame are superimposed. The hydrophobic side chain of Phe is denoted X, since it corresponds to the Kier s dispersion point. (C) 3D model of an idealized sweetener proposed by Tinti and Nofre (1991). Besides the AH-B entity, the model has six additional interaction points connected by a complex network of distances. 

Searching for the perfect artificial sweetener—great taste with no Calories—has been the focus of chemical research for some time. Molecules such as sucralose, aspartamine, and saccharine owe then-sweetness to their size and shape. One theory holds that any sweetener must have three sites that fit into the proper taste buds on the tongue. This theory is appropriately known as the triangle theory. Research artificial sweeteners to develop a model to show how the triangle theory operates. 

Another quantitative sweetener model was developed by Walters and Hinds using genetically evolved receptor models (GERM). The process for GERM development is as follows ... 

Industrially relevant consecutive-competitive reaction schemes on metal catalysts were considered hydrogenation of citral, xylose and lactose. The first case study is relevant for perfumery industry, while the latter ones are used for the production of sweeteners. The catalysts deactivate during the process. The yields of the desired products are steered by mass transfer conditions and the concentration fronts move inside the particles due to catalyst deactivation. The reaction-deactivation-diffusion model was solved and the model was used to predict the behaviours of semi-batch reactors. Depending on the hydrogen concentration level on the catalyst surface, the product distribution can be steered towards isomerization or hydrogenation products. The tool developed in this work can be used for simulation and optimization of stirred tanks in laboratory and industrial scale. 

The important discovery that simple meta-substituted phenylsulphamates (53) are sweet, but not their ortho and para isomers, has been made recently16. Since the discovery of sulphamate sweeteners over 40 years ago it had been tacitly assumed, on the basis of the synthesis and tasting of a few aromatic sulphamates, that phenylsulphamates in which the —NHS03 moiety is directly attached to the aromatic ring are not sweet. The sweetness of these compounds has been simply explained using CPK models and a recently developed theory of sulphamate sweetness90,91 has not proved adequate to explain the sweetness of these novel, new, sweet sulphamates16. 

It is necessary here to consider the type of research which these methods may be used for. Historically, techniques for building models, both physical and mathematical, to relate biologicsd properties to chemical structure have been developed in pharmaceutical and agrochemical research. Many of the examples used in this text are derived from these fields of work. There is no reason, however, why any sort of property which depends on chemical structure should not be modelled in this way. This might be termed quantitative structure-property relationships (QSPR) rather than QSAR where A stands for activity. Such models are beginning to be reported recent examples include applications in the design of dyestuffs, cosmetics, egg-white substitutes, artificial sweeteners, cheese-making, and prepared food products. I have tried to incorporate some of these applications to illustrate the methods, as well as the more traditional examples of QSAR. 

Since the accidental discovery of aspartame in 1965, much effort has been focused on development of an understanding of the biochemical mechanism of sweet taste with the expectation that such knowledge would facilitate the rational design of novel sweeteners with increased stability and potency relative to that of aspartame. To date, although a great deal of inferential data suggests that sweetener receptors are members of the G-protein coupled receptor super family, no sweetener receptor has been isolated or characterized. As a consequence, many sweetener receptor and pharmacophore models have been developed based on the structure-activity relationships (SAR) among known sweeteners. 

Efforts have also been made to develop quantitative sweetener pharmacophore models. Such models allow chemists to predict not only whether or not a compound would be sweet but also the sweetness potency. 

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