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Grant e du bois Grant e du bois Presentation Transcript

  • Grant E DuBoisAdvances in the Science of Sweet Taste & Sweetness Enhancement
  • 2
    Advances in the Science of Sweet Taste & Sweetness Enhancement
    Grant E DuBois
    Research Fellow
    The Coca-Cola Company
    Atlanta, GA
    USA
    The Coca-Cola Company
  • 3
    Outline
    I. Sensing Foods and Beverages
    II. Metrics for Commercial Viability of Sweeteners and Sweetness Enhancers
    III. Sweetness Modulation, aka Optimizing the Tastes of the Non-Caloric Sweeteners of Today
    IV. Sweetener Receptor Positive Allosteric Modulators, a Novel Approach to Sugar-Like Taste
    The Coca-Cola Company
  • The Coca-Cola Company
    4
    I. Sensing Foods & Beverages: Gustation
  • The Coca-Cola Company
    5
    Gustation: A Superimposition of 5 Taste Modalities
    Sweet
    Bitter
    Umami
    Salty
    Sour
  • The Coca-Cola Company
    6
    The Biology of Gustation
  • The Coca-Cola Company
    7
    Lingual Taste Buds are Found in Papillae
  • 8
    Are You a Non-Taster, a Taster or a Supertaster?
    Linda Bartoshuk, U of Florida
    The Coca-Cola Company
  • The Coca-Cola Company
    9
    What Do Taste Buds and Taste Bud Cells Look Like?
    M. Behrens, W. Meyerhof, C. Hellfritsch and T. Hofmann, Angew. Chem. Int. Ed., 2011, 50, 2220-2242.
  • 10
    How do Sweeteners, Bitterants and Savory Compounds Excite Taste Bud Cells?
    Saliva
    Na+
    Na+
    Na+
    Sweetener/
    Bitterant/
    Savory Compound
    Na+
    Receptor
    Na+
    TRP
    Channel
    Electrical
    Message
    to Brain
    Phospholipase C
    Gg
    Gb
    IP2
    IP3
    Ca2+
    Ga
    Cytosol
    ~-60mV
    GDP
    Gg
    Gb
    GTP
    Endoplasmic Reticulum
    The Coca-Cola Company
  • The Coca-Cola Company
    11
    What does the Sweetener Receptor Look Like and How does Sugar Activate it?
    Sucrose
    T1R2
    T1R3
  • 12
    II. Metrics for Commercial Viability of Sweeteners and Sweetness Enhancers
    The Coca-Cola Company
  • 13
    Key Message:
    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.
    The Coca-Cola Company
  • 14
    Commercial Viability is Dependent on 6 Metrics
    Safety
    Taste Quality
    • C/R Function & Rm
    • Flavor Profile
    • Temporal Profile
    • Adaptation Profile
    Stability
    Solubility
    Cost
    Patentability
    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.
    The Coca-Cola Company
  • 15
    III. Sweetness Modulation, aka Optimizing the Tastes of the Non-Caloric Sweeteners of Today
    The Coca-Cola Company
  • 16
    Key Messages:
    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”.
    The Coca-Cola Company
  • MOA Approach to Rebaudioside A Sweetness Modulators
    Operating Principle: The non-sugar-like taste of REBA is intrinsically linked to its chemical structure!
    17
    The Coca-Cola Company
  • MOA Approach to Rebaudioside A Sweetness Modulators (Cont’d)
    • Maruzen Pharmaceutical Company: NaCl found to cause a 2.5-fold increase in potency of stevia sweeteners.
    • 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
    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).
    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: wileyonlinelibrary.com (DOI 10.1002/ffj.2042), Print Version: July-August Issue.
    • Keiko Abe Laboratory (University of Tokyo): Support for the Non-Specific Binding Hypothesis as the rationale for slow sweetness onset and sweetness linger.3
    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.
    18
    The Coca-Cola Company
  • MOA Approach to Rebaudioside A Sweetness Modulators (Cont’d)
    19
    The Coca-Cola Company
    Rebaudioside A (500mg/L) / Osmolyte Formulations
  • 20
    IV. Sweetener Receptor Positive Allosteric Modulators(aka Sweetness Enhancers), a Novel Approach to Sugar-Like Tasteat Lower Calories
    The Coca-Cola Company
  • 21
    Key Message:
    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.
    The Coca-Cola Company
  • Sweetener Receptor Positive Allosteric Modulators
    An Early Conceptual View of the Function of a
    Positive Allosteric Modulator (PAM) in the Sweetener Receptor
    22
    Sucrose
    Signal: 1
    PAM
    Sucrose
    Signal: >>1
    Signal: 0
    Signal: 0
    The Coca-Cola Company
  • Proof of Concept for Sweetness Enhancement
    23
    DHB
    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.
    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: wileyonlinelibrary.com (DOI 10.1002/ffj.2042), Print Version: July-August Issue.
    The Coca-Cola Company
  • Senomyx Collaboration: PAM Discovery by HTS / Cell-Based Assay
    24
    ~8-Fold Sucralose Enhancer
    ~2-Fold Sucrose Enhancer
    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.
    R. Shigemura, C. Podgurski, B. Kitisin, J. Ward, A. Alatorre, PCT Patent Application No. WO2010/014813 A2 (February 4, 2010).
    The Coca-Cola Company
  • 25
    MOA for PAM Activity at the Sweetener Receptor
    Adapted from S. D. Munger et al.
    The Coca-Cola Company
  • Sweetener Receptor PAMs
    26
    • 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!
    • 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.”
    *M. R. Wood, C. Hopkins, J. T. Brogan, P. J. Conn and C. W. Lindsley, Biochemistry2011, 50, 2403-2410.
    The Coca-Cola Company
  • What will be the Future of Sweetener Receptor PAMs?
    • 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?
    *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.
    • Agonist Specificity for Sweetener Receptor PAMs: PAMs reported to date exhibit specificity for individual CHO sweeteners. Can PAMs be identified which enhance all sweeteners?
    • 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?
    • 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?
    27
    The Coca-Cola Company