Using Models to Understand and Design Sweeteners

Walters, D. E.

doi:10.1021/ed072p680

Cited by 25 publications

(16 citation statements)

References 17 publications

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“…A common pharmacophore/ common receptor concept is an explicit or implicit assumption of most efforts, even up until the present day in some cases, to model the relationship between chemical structure and sweet taste. Pharmacophore, receptor as well as computational models for sweet taste were reviewed by Walters [3] and more recently by Temussi [4] and are reviewed here again, now with the advantage of advanced understanding of the human sweetener receptor. A chronology of the most well-known of these is as follows.…”

Section: Gustatory Pharmacophores and Receptors: 20th And 21st Centurmentioning

confidence: 99%

Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models

DuBois

2011

Flavour & Fragrance J

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The relationship between chemical structure and taste has always been a subject of keen interest to chemists. In an effort to rationalize these relationships, chemists have built models, particularly for sweeteners and the sweetener receptor. Early models were exclusively pharmacophore models but, later, receptor models and even computational models with predictive capability were developed. In this paper, models for all the five primary tastes are reviewed. In recent years, the receptors which mediate sweet, bitter and umami (savoury) taste have been identified. The receptors mediating sour and salty tastes, however, are still not known with certainty. The current states of knowledge on the receptors which mediate all five taste modalities are reviewed. Then a perspective is provided on the validity of the models developed. The sequencing of the human genome has enabled great advances in our understanding of the receptors which initiate taste responses. Yet, there remains much we do not understand. A listing of questions still unanswered is provided. Finally, a discussion is provided of new technologies enabled by an advanced understanding of sweetener and bitterant receptors. Specifically, positive allosteric modulators of the sweetener receptor have been identified which enable dramatic reduction in the concentrations of carbohydrate sweeteners while, at the same time, retaining the high quality taste of carbohydrate sweeteners. In addition, bitterness inhibitors have been identified which may have value in the reduction of the negative taste attributes of some foods and beverages. Lastly, an improved understanding of the bio-rationale for the slow sweetness onset and sweetness linger of high-potency sweeteners has led to an approach to improvement of their tastes.

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Section: Gustatory Pharmacophores and Receptors: 20th And 21st Centurmentioning

confidence: 99%

Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models

DuBois

2011

Flavour & Fragrance J

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“…To take into account the chemical nature of the compounds, Temussi and coworkers suggested a more detailed model based on an accurate superposition of rigid sweet compounds, which having few degrees of freedom, should directly reflect the overall shape of the putative receptor cavity (Temussi et al, 1978(Temussi et al, , 1984(Temussi et al, , 1991Kamphuis et al, 1992). This is often referred to as the 'Temussi model' (Walters et al, 1986;Walters, 1995). Figure 1a shows the main contour of the active site hosting a large and rigid sweet compound, 3-anilino-2-styryl-3H-naphtho[1,2-d]imidazole-5-sulphonate.…”

Section: Introductionmentioning

confidence: 99%

The history of sweet taste: not exactly a piece of cake

Temussi

2006

J of Molecular Recognition

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Understanding the molecular bases of sweet taste is of crucial importance not only in biotechnology but also for its medical implications, since an increasing number of people is affected by food-related diseases like, diabetes, hyperlipemia, caries, that are more or less directly linked to the secondary effects of sugar intake. Despite the interest paid to the field, it is only through the recent identification and functional expression of the receptor for sweet taste that new perspectives have been opened, drastically changing our approach to the development of new sweeteners. We shall give an overview of the field starting from the early days up to discussing the newest developments. After a review of early models of the active site, the mechanisms of interaction of small and macromolecular sweet molecules will be examined in the light of accurate modeling of the sweet taste receptor. The analysis of the homology models of all possible dimers allowed by combinations of the human T1R2 and T1R3 sequences of the sweet receptor and the closed (A) and open (B) conformations of the mGluR1 glutamate receptor shows that only 'type B' sites, either T1R2(B) and T1R3(B), can host the majority of small molecular weight sweeteners. Simultaneous binding to the A and B sites is not possible with two large sweeteners but is possible with a small molecule in site A and a large one in site B. This observation accounted for the first time for the peculiar phenomenon of synergy between some sweeteners. In addition to these two sites, the models showed an external binding site that can host sweet proteins.

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“…Previous studies on structure-sweet taste relationships, recently reviewed [7], have been characterized by the glucophore models, starting at the AH-B theory of Shallenberger and Acree [8] and the AH, B, X theory of Kier [9] and moving on to the multipoint attachment theory of Tinti and Nofre [10,11]. These models describe the sweetness of a molecule as arising from functional groups with specific physicochemical properties and, in particular, geometric arrangements.…”

Section: Introductionmentioning

confidence: 99%

Computational studies of sweet-tasting molecules

Barker

Hattotuwagama

Drew

2002

Pure and Applied Chemistry

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Quantitative structure-activity relationships (QSARs) are developed for two separate families of sweet-tasting molecules for which sweetness values relative to sucrose (RS) have been measured. For these two families of sucrose and guanidine derivatives, the molecules were divided into training and test sets. Linear multiple regression equations have been generated to relate separately log(RS) to two types of parameters, namely molecular descriptors and energies derived via molecular field analysis (MFA). The parameters used in the development of linear multiple regression equations were selected by the genetic algorithm. The equations obtained show high predictive quality, which is confirmed by statistical parameters obtained with the test sets.The data for these two families were then combined with data from two other families previously studied, namely the sulfamates and isovanillates, to make a set of 149 compounds. These molecules were also studied by QSAR methods. The generated equations show remarkable predictive power, and the quality of the results suggest that the mechanism of sweet taste receptor is similar and, therefore, that there could well be only one receptor site for sweet taste, particularly for the four sweet taste families considered in this work.

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Using Models to Understand and Design Sweeteners

Cited by 25 publications

References 17 publications

Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models

Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models

The history of sweet taste: not exactly a piece of cake

Computational studies of sweet-tasting molecules

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