Grant e du bois


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Grant e du bois

  1. 1. Grant E DuBoisAdvances in the Science of Sweet Taste & Sweetness Enhancement<br />
  2. 2. 2<br />Advances in the Science of Sweet Taste & Sweetness Enhancement<br />Grant E DuBois<br />Research Fellow<br />The Coca-Cola Company<br />Atlanta, GA <br />USA<br />The Coca-Cola Company<br />
  3. 3. 3<br />Outline<br />I. Sensing Foods and Beverages<br />II. Metrics for Commercial Viability of Sweeteners and Sweetness Enhancers<br />III. Sweetness Modulation, aka Optimizing the Tastes of the Non-Caloric Sweeteners of Today<br />IV. Sweetener Receptor Positive Allosteric Modulators, a Novel Approach to Sugar-Like Taste<br />The Coca-Cola Company<br />
  4. 4. The Coca-Cola Company<br />4<br />I. Sensing Foods & Beverages: Gustation<br />
  5. 5. The Coca-Cola Company<br />5<br />Gustation: A Superimposition of 5 Taste Modalities <br />Sweet<br />Bitter<br />Umami <br />Salty<br />Sour<br />
  6. 6. The Coca-Cola Company<br />6<br />The Biology of Gustation<br />
  7. 7. The Coca-Cola Company<br />7<br />Lingual Taste Buds are Found in Papillae<br />
  8. 8. 8<br />Are You a Non-Taster, a Taster or a Supertaster?<br />Linda Bartoshuk, U of Florida<br />The Coca-Cola Company<br />
  9. 9. The Coca-Cola Company<br />9<br />What Do Taste Buds and Taste Bud Cells Look Like?<br />M. Behrens, W. Meyerhof, C. Hellfritsch and T. Hofmann, Angew. Chem. Int. Ed., 2011, 50, 2220-2242.<br />
  10. 10. 10<br />How do Sweeteners, Bitterants and Savory Compounds Excite Taste Bud Cells?<br />Saliva<br />Na+<br />Na+<br />Na+<br />Sweetener/<br />Bitterant/<br />Savory Compound<br />Na+<br />Receptor<br />Na+<br />TRP<br />Channel<br />Electrical<br /> Message <br />to Brain<br />Phospholipase C<br />Gg<br />Gb<br />IP2<br />IP3<br />Ca2+<br />Ga<br />Cytosol<br />~-60mV<br />GDP<br />Gg<br />Gb<br />GTP<br />Endoplasmic Reticulum<br />The Coca-Cola Company<br />
  11. 11. The Coca-Cola Company<br />11<br />What does the Sweetener Receptor Look Like and How does Sugar Activate it? <br />Sucrose<br />T1R2<br />T1R3<br />
  12. 12. 12<br />II. Metrics for Commercial Viability of Sweeteners and Sweetness Enhancers<br />The Coca-Cola Company<br />
  13. 13. 13<br />Key Message: <br />In order to realize outstanding commercial success, a new sweetness technology must deliver on all of the metrics........Safety, Taste Quality, Stability, Solubility and Cost…… and without compromise on Safety or Taste Quality.<br />The Coca-Cola Company<br />
  14. 14. 14<br />Commercial Viability is Dependent on 6 Metrics<br />Safety<br />Taste Quality<br /><ul><li>C/R Function & Rm
  15. 15. Flavor Profile
  16. 16. Temporal Profile
  17. 17. Adaptation Profile</li></ul>Stability<br />Solubility<br />Cost<br />Patentability<br />G. E. DuBois, “Sweeteners and Sweetness Modulators: Requirements for Commercial Viability”, Chapter 29 in Sweetness and Sweeteners, G E DuBois and D Weerasinghe, Eds., ACS Symposium Series 979, ACS Books, Washington DC, 2008.<br />The Coca-Cola Company<br />
  18. 18. 15<br />III. Sweetness Modulation, aka Optimizing the Tastes of the Non-Caloric Sweeteners of Today<br />The Coca-Cola Company<br />
  19. 19. 16<br />Key Messages: <br />1. HP sweeteners known today do not match the Taste Quality of sugar……….anddelivery on the Taste Quality metric requires “Sweetness Modulators”; and 2. Since trial-and-error approaches have been employed for saccharin (>100 years) and aspartame (~30 years) w/o significant progress……..a new paradigm……..a Mechanism of Action (MOA) based paradigm………is needed to find effective “Sweetness Modulators”.<br />The Coca-Cola Company<br />
  20. 20. MOA Approach to Rebaudioside A Sweetness Modulators<br />Operating Principle: The non-sugar-like taste of REBA is intrinsically linked to its chemical structure! <br />17<br />The Coca-Cola Company<br />
  21. 21. MOA Approach to Rebaudioside A Sweetness Modulators (Cont’d)<br /><ul><li>Maruzen Pharmaceutical Company: NaCl found to cause a 2.5-fold increase in potency of stevia sweeteners.
  22. 22. The Coca-Cola Company: NaCl, and/or other osmolytes, found to cause increases in sweetness potencies as well as elimination of the slow sweetness onset and the sweetness linger for Rebaudioside A and other HP sweeteners thus leading to the Non-Specific Binding Hypothesis.1, 2</li></ul>1. I. Prakash, G. E. DuBois, P. Jella, G. A. King, R. I. San Miguel, K. H. Sepcic, D. K. Weerasinghe, N. R. White, US Patent Application 20070128311 (June 7, 2007).<br />2. G. DuBois, “Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models” Flavour and Fragrance Journal 2011, Electronic Version: (DOI 10.1002/ffj.2042), Print Version: July-August Issue.<br /><ul><li>Keiko Abe Laboratory (University of Tokyo): Support for the Non-Specific Binding Hypothesis as the rationale for slow sweetness onset and sweetness linger.3</li></ul>3. K. Abe, et al., “Surface Plasmon Resonance Analysis on Interactions of Food Components with a Taste Epithelial Cell Model”, J. Agric. Fd. Chem. 2010, 58 (22), 11870-11875.<br />18<br />The Coca-Cola Company<br />
  23. 23. MOA Approach to Rebaudioside A Sweetness Modulators (Cont’d)<br />19<br />The Coca-Cola Company<br />Rebaudioside A (500mg/L) / Osmolyte Formulations<br />
  24. 24. 20<br />IV. Sweetener Receptor Positive Allosteric Modulators(aka Sweetness Enhancers), a Novel Approach to Sugar-Like Tasteat Lower Calories<br />The Coca-Cola Company<br />
  25. 25. 21<br />Key Message: <br />Sweetener receptor positive allosteric modulators (PAMs)…..……aka enhancers…….which potentiate the activities of carbohydrate sweeteners enable accurate reproduction of carbohydrate sweetener taste quality w/ dramatic reduction in caloric content.<br />The Coca-Cola Company<br />
  26. 26. Sweetener Receptor Positive Allosteric Modulators<br />An Early Conceptual View of the Function of a <br />Positive Allosteric Modulator (PAM) in the Sweetener Receptor<br />22<br />Sucrose<br />Signal: 1<br />PAM<br />Sucrose<br />Signal: >>1<br />Signal: 0<br />Signal: 0<br />The Coca-Cola Company<br />
  27. 27. Proof of Concept for Sweetness Enhancement<br />23<br />DHB<br />2001: @ 375 mg/L, DHB enhances 6% sucrose to 8% sucrose w/o any off taste! A weaker effect was noted for fructose and no effect for glucose.<br />G. DuBois, “Validity of early indirect models of taste active sites and advances in new taste technologies enabled by improved models” Flavour and Fragrance Journal 2011, Electronic Version: (DOI 10.1002/ffj.2042), Print Version: July-August Issue.<br />The Coca-Cola Company<br />
  28. 28. Senomyx Collaboration: PAM Discovery by HTS / Cell-Based Assay<br />24<br />~8-Fold Sucralose Enhancer<br />~2-Fold Sucrose Enhancer<br />G. Servant, C. Tachdjian, X. Tang, S. Werner, F. Zhang, X. Li, P. Kamdar, G. Petrovic, T. Ditschun, A. Java, P. Brust, N. Brune, G. E. DuBois, M. Zoller and D. S. Karanewsky, Proc. Natl. Acad. Sci. USA, 2010, 107, 4746-4751.<br />R. Shigemura, C. Podgurski, B. Kitisin, J. Ward, A. Alatorre, PCT Patent Application No. WO2010/014813 A2 (February 4, 2010).<br />The Coca-Cola Company<br />
  29. 29. 25<br />MOA for PAM Activity at the Sweetener Receptor<br />Adapted from S. D. Munger et al.<br />The Coca-Cola Company<br />
  30. 30. Sweetener Receptor PAMs<br />26<br /><ul><li>Original Hypothesis: CHO Sweetener / PAM formulations will taste equivalent to CHO Sweeteners (i.e., not be limited by low Rm, bitter, metallic, licorice, etc. off tastes, slow sweetness onset / sweetness linger and sweetness adaptation; observations to date support that this hypothesis is correct!
  31. 31. Wood et al. 2011 Review:* “A PAM will exert its effects only when the endogenous agonist is present, resulting in temporal and spatial activity of the endogenous ligand.”</li></ul> *M. R. Wood, C. Hopkins, J. T. Brogan, P. J. Conn and C. W. Lindsley, Biochemistry2011, 50, 2403-2410.<br />The Coca-Cola Company<br />
  32. 32. What will be the Future of Sweetener Receptor PAMs?<br /><ul><li>Efficacy of Sweetener Receptor PAMs: Ma et al.,* have reported GPCR PAMs w/ >100-fold enhancements. Can 100-fold enhancers be found for the sweetener receptor?</li></ul>*L. Ma, M. Seager, M. Wittmann, M. Jacobson, D. Bickel, M. Burno, K. Jones, V. KuzmickGraufelds, G. Xu, M. Pearson, A. McCampbell, R. Gaspar, P. Shughrue, A. Danziger, C. Regan, R. Flick, D. Pascarella, S. Garson, S. Doran, C. Kreatsoulas, L. Veng, C. W. Lindsley, W. Shipe, S. Kuduk, C. Sur, G. Kinney, G. R. Seabrook, W. J. Ray, Proc. Natl. Acad. Sci. USA 2009, 106, 15950-15955.<br /><ul><li>Agonist Specificity for Sweetener Receptor PAMs: PAMs reported to date exhibit specificity for individual CHO sweeteners. Can PAMs be identified which enhance all sweeteners?
  33. 33. Natural PAMs: PAMs reported to date are synthetic compounds which are being developed as artificial flavors. Can commercially-viable natural enhancers be found which can be labeled as natural flavors?
  34. 34. PAMs for Natural High-Potency Sweeteners: PAMs for stevia sweeteners would enable their use at lower concentrations which may help address their negative taste attributes. Can commercially-viableenhancers for stevia and other natural high-potency sweeteners be found?</li></ul>27<br />The Coca-Cola Company<br />